75 results on '"Gasperowicz P"'
Search Results
2. Association between social relationship of mentors and depressive symptoms in first-time mothers during the transition from pregnancy to 6-months postpartum
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Malgorzata Gasperowicz and Karen M. Benzies
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First-time mothers ,Postpartum ,Depressive symptoms ,Mentorship ,Social support ,Medicine - Abstract
Abstract Background First-time motherhood is characterized by high psychosocial distress, which untreated, has serious consequences. Informal social support provided by specially trained mentors may be protective against postpartum depressive symptoms but may vary by women’s social relationship with the mentor. The objective of this study was to evaluate the association of types of mentors on women’s depressive symptoms between late pregnancy to 6-months postpartum and the characteristics of women associated with mentor type. Methods This study was a secondary analysis of data from a community sample of 312 primiparous women from a single-group, longitudinal intervention study of Welcome to Parenthood. Welcome to Parenthood provided education and mentorship for women during the transition from pregnancy to postpartum. Women completed the Edinburgh Postnatal Depression Scale (EPDS) in late pregnancy, and 2- and 6-months postpartum. Results Women who recently relocated were less likely to be mentored by their mothers and more likely to be mentored by friends or volunteers. Women who were mentored by their mothers or sisters scored the lowest on the EPDS; those mentored by their mothers-in-law scored the highest. Women who were mentored by other family, friends, or volunteers scored between the two extremes. EPDS scores of women mentored by each type of mentor decreased from pregnancy to 6-months postpartum; only for mother-, sister-, and volunteer-mentored groups was this decrease significant. Conclusions During transition to parenthood, support provided by mothers or sisters is best for women’s mental health but may not always be available to women who have recently relocated. In such situations, specially trained community volunteers may be the second-best option.
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- 2024
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3. Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome
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Doriana Misceo, Lokuliyanage Dona Samudita Senaratne, Inger-Lise Mero, Arvind Y. M. Sundaram, Pål Marius Bjørnstad, Krzysztof Szczałuba, Piotr Gasperowicz, Benjamin Kamien, Bård Nedregaard, Asbjørn Holmgren, Petter Strømme, and Eirik Frengen
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CENPF ,ciliopathy ,intestinal atresia ,LR-WGS ,structural variant ,Strømme syndrome ,Genetics ,QH426-470 - Abstract
Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, we identified novel pathogenic variants in CENPF, including one structural variant, giving a genetic diagnosis to the patients. Patient 1 was a premature baby who died at 26 days with congenital malformations affecting many organs including the brain, eyes, and intestine. She was homozygous for a donor splice variant in CENPF, NM_016343.3:c.1068+1G>A, causing skipping of exon 7, resulting in a frameshift. Patient 2 was a female with intestinal atresia, microcephaly, and a Peters anomaly. She had normal developmental milestones at the age of 7 years. She is compound heterozygous for CENPF NM_016343.3:c.5920dup and c.8991del, both frameshift. Patient 3 was a male with anomalies of the brain, eye, intestine, and kidneys. He was compound heterozygous for CENPF p.(Glu298Ter), and a 5323 bp deletion covering exon 1. CENPF exon 1 is flanked by repetitive sequences that may represent a site of a recurrent structural variation, which should be a focus in patients with Strømme syndrome of unknown etiology.
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- 2023
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4. Epigenetic Findings in Twins with Esophageal Atresia
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Michal Błoch, Piotr Gasperowicz, Sylwester Gerus, Katarzyna Rasiewicz, Arleta Lebioda, Pawel Skiba, Rafal Płoski, Dariusz Patkowski, Pawel Karpiński, and Robert Śmigiel
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esophageal atresia ,Rho signaling pathway ,epigenetics ,methylation ,rare disease ,genomics ,Genetics ,QH426-470 - Abstract
Esophageal atresia (EA) is the most common malformation of the upper gastrointestinal tract. The estimated incidence of EA is 1 in 3500 births. EA is more frequently observed in boys and in twins. The exact cause of isolated EA remains unknown; a multifactorial etiology, including epigenetic gene expression modifications, is considered. The study included six pairs of twins (three pairs of monozygotic twins and three pairs of dizygotic twins) in which one child was born with EA as an isolated defect, while the other twin was healthy. DNA samples were obtained from the blood and esophageal tissue of the child with EA as well as from the blood of the healthy twin. The reduced representation bisulfite sequencing (RRBS) technique was employed for a whole-genome methylation analysis. The analyses focused on comparing the CpG island methylation profiles between patients with EA and their healthy siblings. Hypermethylation in the promoters of 219 genes and hypomethylation in the promoters of 78 genes were observed. A pathway enrichment analysis revealed the statistically significant differences in methylation profile of 10 hypermethylated genes in the Rho GTPase pathway, previously undescribed in the field of EA (ARHGAP36, ARHGAP4, ARHGAP6, ARHGEF6, ARHGEF9, FGD1, GDI1, MCF2, OCRL, and STARD8).
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- 2023
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5. Methylation Genome-Wide Profiling in Lowly and Highly Efficient Somatic Cell Nuclear Transfer in Pigs
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Maciej Grzybek, Krzysztof Flisikowski, Tom Giles, Marta Dyjak, Rafal Ploski, Piotr Gasperowicz, Richard D. Emes, and Pawel Lisowski
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SCNT ,RRBS ,AMSC ,DNA methylation ,epigenetics ,epigenomics ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Swine is a common model organism for biomedical research. Epigenetic reprogramming in somatic cell nuclear transfer (SCNT) embryos does not fully recapitulate the natural DNA demethylation events at fertilisation. This study aimed to conduct genome-wide methylation profiling to detect differentially methylated regions (DMRs) responsible for epigenetic differences in stem cells that displayed high and low efficiency of SCNT and to elucidate the low efficiency of cloning rate in pigs. Adipose tissue mesenchymal stem cells (AMSC)s lines were isolated from adipose tissue of adult male pigs (n = 20; high-efficiency cells = 10; and low-efficiency cells = 10). Reduced representation bisulfite sequencing (RRBS) was performed on an Illumina HiSeq1500. Paired-end reads were filtered to remove the adapter contamination, and low-quality reads using TrimGalore! Filtered reads were mapped to the reference genome using Bismark. MethylKit was used to identify differentially methylated regions (DMRs) (bases and tiles), showing statistically significant differential methylation between high and low-efficiency AMSCs. Hierarchical cluster analysis according to methylation patterns clearly defined groups with low and high cloning efficiency. We report 3704 bases with statistically significant differences in methylation and 10062 tiles with statistically significant differences in methylation. Most differentially methylated sites are intergenic 62%, 31% are intronic, 4% are in exons, and 4% in promoters. Moreover, 37% of differentially methylated sites are located in known CpG islands (CGIs), and 4% in CpG island shores (CGSs).
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- 2023
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6. Welcome to Parenthood is associated with reduction of postnatal depressive symptoms during the transition from pregnancy to 6 months postpartum in a community sample: a longitudinal evaluation
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Benzies, Karen M., Gasperowicz, Malgorzata, Afzal, Arfan, and Loewen, Melody
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- 2021
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7. Allogenic Adipose-Derived Stem Cells in Diabetic Foot Ulcer Treatment: Clinical Effectiveness, Safety, Survival in the Wound Site, and Proteomic Impact
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Beata Mrozikiewicz-Rakowska, Ilona Szabłowska-Gadomska, Dominik Cysewski, Stefan Rudziński, Rafał Płoski, Piotr Gasperowicz, Magdalena Konarzewska, Jakub Zieliński, Mateusz Mieczkowski, Damian Sieńko, Tomasz Grzela, Maria Noszczyk, Barbara Paleska, Leszek Czupryniak, and Malgorzata Lewandowska-Szumiel
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cell therapy ,diabetic foot ulcer ,adipose-derived stem cells ,ADSC ,ATMP ,proteomics ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism of action has been studied mainly in vitro and in animals. This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound. Equal groups of 23 participants each received fibrin gel with ADSCs or fibrin gel alone. The clinical effects were assessed at four time points: days 7, 14, 21 and 49. Material collected during debridement from a subset of each group was analyzed for the presence of ADSC donor DNA and proteomic changes. The reduction in wound size was greater at all subsequent visits, significantly on day 21 and 49, and the time to 50% reduction in the wound size was significantly shorter in patients who received ADSCs. Complete healing was achieved at the end of the study in seven patients treated with ADSCs vs. one treated without ADSCs. One week after ADSC application, 34 proteins significantly differentiated the material from both groups, seven of which, i.e., GAPDH, CAT, ACTN1, KRT1, KRT9, SCL4A1, and TPI, positively correlated with the healing rate. We detected ADSC donor DNA up to 21 days after administration. We confirmed ADSC-related improvement in wound healing that correlated with the molecular background, which provides insights into the role of ADSCs in wound healing—a step toward the development of cell-based therapies.
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- 2023
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8. Intracardiac tumor as a rare manifestation of genetic syndromes—presentation of a family with Gorlin syndrome and a literature review
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Szczałuba, Krzysztof, Makuła, Ewa, Piórecka-Makuła, Anna, Sicińska, Justyna, Rydzanicz, Małgorzata, Gasperowicz, Piotr, Płoski, Rafał, and Werner, Bożena
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- 2020
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9. Occurrence of Esophageal Atresia With Tracheoesophageal Fistula in Siblings From Three-Generation Family Affected by Variable Expressivity MYCN Mutation: A Case Report
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Magdalena Klaniewska, Krystian Toczewski, Anna Rozensztrauch, Michal Bloch, Agata Dzielendziak, Piotr Gasperowicz, Ryszard Slezak, Rafał Ploski, Małgorzata Rydzanicz, Robert Smigiel, and Dariusz Patkowski
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esophageal atresia ,tracheoesophageal fistula ,MYCN ,Feingold syndrome ,familial occurrence ,Pediatrics ,RJ1-570 - Abstract
The MYCN oncogene encodes a transcription factor belonging to the MYC family. It is primarily expressed in normal developing embryos and is thought to be critical in brain and other neural development. Loss-of-function variants resulting in haploinsufficiency of MYCN, which encodes a protein with a basic helix–loop–helix domain causes Feingold syndrome (OMIM 164280, ORPHA 391641). We present an occurrence of esophageal atresia (EA) with tracheoesophageal fistula in siblings from a three-generation family affected by variable expressivity of MYCN mutation p.(Ser90GlnfsTer176) as a diagnostic effect of searching the cause of familial esophageal atresia using NGS-based whole-exome sequencing (WES). All of our affected patients showed microcephaly and toe syndactyly, which were frequently reported in the literature. Just one patient exhibited clinodactyly. None of the patients exhibited brachymesophalangy or hypoplastic thumbs. The latest report noted that patients with EA and Feingold syndrome were also those with the more complex and severe phenotype. However, following a thorough review of the present literature, the same association was not found, which is also confirmed by the case we described. The variable phenotypic expression of the patients we described and the data from the literature guide a careful differential diagnosis of Feingold syndrome even in cases of poorly expressed and non-specific symptoms.
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- 2021
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10. Defining the clinical-genetic and neuroradiological features in SPG54: description of eight additional cases and nine novel DDHD2 variants
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Nicita, Francesco, Stregapede, Fabrizia, Tessa, Alessandra, Bassi, Maria Teresa, Jezela-Stanek, Aleksandra, Primiano, Guido, Pizzuti, Antonio, Barghigiani, Melissa, Nardella, Marta, Zanni, Ginevra, Servidei, Serenella, Astrea, Guja, Panzeri, Elena, Maghini, Cristina, Losito, Luciana, Ploski, Rafal, Gasperowicz, Piotr, Santorelli, Filippo Maria, Bertini, Enrico, and Travaglini, Lorena
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- 2019
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11. Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
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Agnieszka Stembalska, Małgorzata Rydzanicz, Wojciech Walas, Piotr Gasperowicz, Agnieszka Pollak, Victor Murcia Pienkowski, Mateusz Biela, Magdalena Klaniewska, Zuzanna Gamrot, Ewa Gronska, Rafal Ploski, and Robert Smigiel
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infantile hypotonia ,respiratory failure syndrome ,SMARD ,LAS1L gene ,Genetics ,QH426-470 - Abstract
LAS1L encodes a nucleolar ribosomal biogenesis protein and is also a component of the Five Friends of Methylated CHTOP (5FMC) complex. Mutations in the LAS1L gene can be associated with Wilson–Turner syndrome (WTS) and, much more rarely, severe infantile hypotonia with respiratory failure. Here, we present an eighteen-month old boy with a phenotype of spinal muscular atrophy with respiratory distress (SMARD). By applying WES, we identified a novel hemizygous synonymous variant in the LAS1L gene inherited from an unaffected mother (c.846G > C, p.Thr282=). We suggest that the identified variant impairs the RNA splicing process. Furthermore, we proved the absence of any coding regions by qPCR and sequencing cDNA using amplicon deep sequencing and Sanger sequencing methods. According to the SMARD phenotype, severe breathing problems causing respiratory insufficiency, hypotonia, and feeding difficulties were observed in our patient from the first days of life. Remarkably, our case is the second described patient with a SMARD-like phenotype due to a mutation in the LAS1L gene and the first with a variant impacting splicing.
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- 2022
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12. Novel de novo mutation affecting two adjacent aminoacids in the EED gene in a patient with Weaver syndrome
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Smigiel, Robert, Biernacka, Anna, Biela, Mateusz, Murcia-Pienkowski, Victor, Szmida, Elzbieta, Gasperowicz, Piotr, Kosinska, Joanna, Kostrzewa, Grazyna, Koppolu, Agnieszka Anna, Walczak, Anna, Wawrzuta, Dominik, Rydzanicz, Malgorzata, Sasiadek, Malgorzata, and Ploski, Rafal
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- 2018
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13. A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy – a case report and review of the genotype–phenotype correlation
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Agnieszka A. Koppolu, Agnieszka Madej-Pilarczyk, Małgorzata Rydzanicz, Joanna Kosińska, Piotr Gasperowicz, Jolanta Dorszewska, Wojciech Kozubski, Barbara Steinborn, Andrzej M. Kochański, and Rafał Płoski
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COL6A1 ,RNA splicing ,Bethlem myopathy ,Medicine - Abstract
Collagen VI-related myopathy is a group of disorders affecting skeletal muscles and connective tissue. The most common symptoms are muscle weakness and joint deformities which limit the movement and progress over time. Several forms of collagen VI-related myopathies have been described: Bethlem myopathy, an intermediate form and Ullrich congenital muscular dystrophy, which is the most severe. Here we report a novel de novo c.1056+3A>C substitution in intron 14 of the COL6A1 gene encoding alpha-chains of collagen VI in a 13-year-old girl suffering from collagen VI (ColVI) myopathy. Analysis performed on cDNA generated from the RNA obtained from the patient’s blood cells showed that the reported variant leads to the entire exon 14 skipping and probably results in an in-frame deletion of 18 amino acids of the COL6A1 protein. Clinical presentation, abnormal secretion of the collagen demonstrated in muscle biopsy and the COL6A1 c.1056+3A>C mutation justify classification of the presented case as ColVI myopathy with moderate-progressive course. Analysis of the literature indicates that the donor splice site of COL6A1 intron 14, associated with the phenotype of Bethlem myopathy or intermediate form, is a hot spot for ColVI myopathies.
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- 2017
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14. Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
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Grażyna T. Truszkowska, Zofia T. Bilińska, Angelika Muchowicz, Agnieszka Pollak, Anna Biernacka, Katarzyna Kozar-Kamińska, Piotr Stawiński, Piotr Gasperowicz, Joanna Kosińska, Tomasz Zieliński, and Rafał Płoski
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Medicine ,Science - Abstract
Abstract The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband’s brother. The expression of the NRAP protein was undetectable in the patient’s heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.
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- 2017
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15. Mild Zellweger syndrome due to a novel PEX6 mutation: correlation between clinical phenotype and in silico prediction of variant pathogenicity
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Rydzanicz, Małgorzata, Stradomska, Teresa Joanna, Jurkiewicz, Elżbieta, Jamroz, Ewa, Gasperowicz, Piotr, Kostrzewa, Grażyna, Płoski, Rafał, and Tylki-Szymańska, Anna
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- 2017
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16. Leukoencephalopathy with Calcifications and Cysts—The First Polish Patient with Labrune Syndrome
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Magdalena Machnikowska-Sokołowska, Jacek Pilch, Justyna Paprocka, Małgorzata Rydzanicz, Agnieszka Pollak, Joanna Kosińska, Piotr Gasperowicz, Katarzyna Gruszczyńska, Ewa Emich-Widera, and Rafał Płoski
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Labrune syndrome ,SNORD118 gene ,magnetic resonance imaging ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Leukoencephalopathy with calcifications and cysts (LCC) is a triad of neuroradiological symptoms characteristic of Labrune syndrome, which was first described in 1996. For 20 years, the diagnosis was only based on clinical, neuroradiological and histopathological findings. Differential diagnosis included a wide spectrum of diseases. Finally, in 2016, genetic mutation in the SNORD118 gene was confirmed to cause Labrune syndrome. The authors describe a case of a teenage girl with progressive headaches, without developmental delay, presenting with calcifications and white matter abnormality in neuroimaging. Follow-up studies showed the progression of leukoencephalopathy and cyst formation. The first symptoms and initial imaging results posed diagnostic challenges. The final diagnosis was established based on genetic results. The authors discuss the possible therapy of LCC with Bevacizumab.
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- 2020
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17. Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit
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Robert Śmigiel, Mateusz Biela, Krzysztof Szmyd, Michal Błoch, Elżbieta Szmida, Paweł Skiba, Anna Walczak, Piotr Gasperowicz, Joanna Kosińska, Małgorzata Rydzanicz, Piotr Stawiński, Anna Biernacka, Marzena Zielińska, Waldemar Gołębiowski, Agnieszka Jalowska, Grażyna Ohia, Bożena Głowska, Wojciech Walas, Barbara Królak-Olejnik, Paweł Krajewski, Jolanta Sykut-Cegielska, Maria M. Sąsiadek, and Rafał Płoski
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WES ,pediatric intensive care unit ,genetic disorders ,NGS ,novel diseases ,first-tier tests ,Medicine - Abstract
Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5–14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (NARS1 and DCAF5). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling.
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- 2020
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18. The construction of the Gilmore–Perelomov coherent states for the Kratzer–Fues anharmonic oscillator with the use of the algebraic approach
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Mikulski, Damian, Gasperowicz, Daniel, and Konarski, Jerzy
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- 2015
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19. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.
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Paula N Gonzalez, Malgorzata Gasperowicz, Jimena Barbeito-Andrés, Natasha Klenin, James C Cross, and Benedikt Hallgrímsson
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Medicine ,Science - Abstract
Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth.
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- 2016
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20. Simplified method for gene targeting vector construction
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Malgorzata Gasperowicz, Mateusz Kolanczyk, Michael Stock, and Florian Otto
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Biology (General) ,QH301-705.5 - Published
- 2004
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21. Definitional and Methodological Errors in Pediatric Post–COVID-19 Condition Research Letter
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Murdoch, Blake, Gasperowicz, Malgorzata, and Ungrin, Mark
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- 2024
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22. A de novo loss-of-function DYNC1H1 mutation in a patient with parkinsonian features and a favourable response to levodopa
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Szczałuba, K., primary, Szymańska, K., additional, Rydzanicz, M., additional, Ciara, E., additional, Walczak, A., additional, Piekutowska-Abramczuk, D., additional, Kosińska, J., additional, Jacoszek, A., additional, Czerska, K., additional, Biernacka, A., additional, Laure-Kamionowska, M., additional, Gasperowicz, P., additional, Pronicka, E., additional, and Płoski, R., additional
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- 2017
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23. Broad clinical spectrum observed in patients with scapuloperoneal spinal muscular atrophy (SPSMA) caused by an c.806G > A (p. Arg269His) mutation in the TRPV4 gene
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Jędrzejowska, M., primary, Dębek, E., additional, Halat, P., additional, Kostera-Pruszczyk, A., additional, Jezela-Stanek, A., additional, Ciara, E., additional, Rydzanicz, M., additional, Gasperowicz, P., additional, and Gos, M., additional
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- 2017
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24. DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups
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Spólnicka, M., primary, Pośpiech, E., additional, Pepłońska, B., additional, Zbieć-Piekarska, R., additional, Makowska, Ż., additional, Pięta, A., additional, Karłowska-Pik, J., additional, Ziemkiewicz, B., additional, Wężyk, M., additional, Gasperowicz, P., additional, Bednarczuk, T., additional, Barcikowska, M., additional, Żekanowski, C., additional, Płoski, R., additional, and Branicki, Wojciech, additional
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- 2017
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25. DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups.
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Spólnicka, M., Pośpiech, E., Pepłońska, B., Zbieć-Piekarska, R., Makowska, Ż., Pięta, A., Karłowska-Pik, J., Ziemkiewicz, B., Wężyk, M., Gasperowicz, P., Bednarczuk, T., Barcikowska, M., Żekanowski, C., Płoski, R., and Branicki, Wojciech
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DNA methylation ,FORENSIC sciences ,AGE determination of human beings ,ALZHEIMER'S patients ,ARTIFICIAL neural networks - Abstract
Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions. The obtained results showed that the selected age-related CpG sites have unchanged age prediction capacity in the group of late onset Alzheimer's disease patients. Aberrant hypermethylation and decreased prediction accuracy were found for TRIM59 and KLF14 markers in the group of early onset Alzheimer's disease suggesting accelerated aging of patients. In the Graves' disease patients, altered DNA methylation profile and modified age prediction accuracy were noted for TRIM59 and FHL2 with aberrant hypermethylation observed for the former and aberrant hypomethylation for the latter. Our work emphasizes high utility of the ELOVL2 and C1orf132 markers for prediction of chronological age in forensics by showing unchanged prediction accuracy in individuals affected by three diseases. The study also demonstrates that artificial neural networks could be a convenient alternative for the forensic predictive DNA analyses. [ABSTRACT FROM AUTHOR]
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- 2018
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26. P.128 - Broad clinical spectrum observed in patients with scapuloperoneal spinal muscular atrophy (SPSMA) caused by an c.806G > A (p. Arg269His) mutation in the TRPV4 gene
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Jędrzejowska, M., Dębek, E., Halat, P., Kostera-Pruszczyk, A., Jezela-Stanek, A., Ciara, E., Rydzanicz, M., Gasperowicz, P., and Gos, M.
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- 2017
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27. Novel de novo mutation affecting two adjacent aminoacids in the EEDgene in a patient with Weaver syndrome
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Smigiel, Robert, Biernacka, Anna, Biela, Mateusz, Murcia-Pienkowski, Victor, Szmida, Elzbieta, Gasperowicz, Piotr, Kosinska, Joanna, Kostrzewa, Grazyna, Koppolu, Agnieszka Anna, Walczak, Anna, Wawrzuta, Dominik, Rydzanicz, Malgorzata, Sasiadek, Malgorzata, and Ploski, Rafal
- Abstract
Overgrowth, macrocephaly, accelerated osseous maturation, variable intellectual disability, and characteristic facial features are the main symptoms of Weaver syndrome, a rare condition caused by mutations in EZH2gene. Recently, in four patients with Weaver-like symptoms without mutations in EZH2gene, pathogenic variants in EEDwere described. We present another patient clinically diagnosed with Weaver syndrome in whom WES revealed an EEDde novo mutation affecting two neighboring aminoacids, NM_003797.3:c.917_919delinsCGG/p.(Arg306_Asn307delinsThrAsp) located in one allele (in cis). Our observation, together with previous reports suggests that EEDgene testing is warranted in patients with the overgrowth syndrome features and suspicion of Weaver syndrome with normal results of EZH2gene sequencing.
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- 2018
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28. Dominant ELOVL1mutation causes neurological disorder with ichthyotic keratoderma, spasticity, hypomyelination and dysmorphic features
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Kutkowska-Kaźmierczak, Anna, Rydzanicz, Małgorzata, Chlebowski, Aleksander, Kłosowska-Kosicka, Kamila, Mika, Adriana, Gruchota, Jakub, Jurkiewicz, Elźżbieta, Kowalewski, Cezary, Pollak, Agnieszka, Stradomska, Teresa Joanna, Kmieźżć, Tomasz, Jakubowski, Rafał, Gasperowicz, Piotr, Walczak, Anna, źżćŚladowski, Dariusz, Jankowska-Steifer, Ewa, Korniszewski, Lech, KosiźżćŚńska, Joanna, Obersztyn, Ewa, Nowak, Wieslaw, źżćŚńŚledziźżćŚńŚński, Tomasz, Dziembowski, Andrzej, and Płoski, Rafał
- Abstract
BackgroundIchthyosis and neurological involvement occur in relatively few known Mendelian disorders caused by mutations in genes relevant both for epidermis and neural function.ObjectivesTo identify the cause of a similar phenotype of ichthyotic keratoderma, spasticity, mild hypomyelination (on MRI) and dysmorphic features (IKSHD) observed in two unrelated paediatric probands without family history of disease.MethodsWhole exome sequencing was performed in both patients. The functional effect of prioritised variant in ELOVL1 (very-long-chain fatty acids (VLCFAs) elongase) was analysed by VLCFA profiling by gas chromatography–mass spectrometry in stably transfected HEK2932 cells and in cultured patient’s fibroblasts.ResultsProbands shared novel heterozygous ELOVL1p.Ser165Phe mutation (de novo in one family, while in the other family, father could not be tested). In transfected cells p.Ser165Phe: (1) reduced levels of FAs C24:0-C28:0 and C26:1 with the most pronounced effect for C26:0 (P=7.8×10−6 vs HEK293 cells with wild type (wt) construct, no difference vs naive HEK293) and (2) increased levels of C20:0 and C22:0 (P=6.3×10−7, P=1.2×10−5, for C20:0 and C22:0, respectively, comparison vs HEK293 cells with wt construct; P=2.2×10−7, P=1.9×10−4, respectively, comparison vs naive HEK293). In skin fibroblasts, there was decrease of C26:1 (P=0.014), C28:0 (P=0.001) and increase of C20:0 (P=0.033) in the patient versus controls. There was a strong correlation (r=0.92, P=0.008) between the FAs profile of patient’s fibroblasts and that of p.Ser165Phe transfected HEK293 cells. Serum levels of C20:0–C26:0 FAs were normal, but the C24:0/C22:0 ratio was decreased.ConclusionThe ELOVL1p.Ser165Phe mutation is a likely cause of IKSHD.
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- 2018
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29. Mild Zellweger syndrome due to a novel PEX6mutation: correlation between clinical phenotype and in silico prediction of variant pathogenicity
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Rydzanicz, Małgorzata, Stradomska, Teresa, Jurkiewicz, Elżbieta, Jamroz, Ewa, Gasperowicz, Piotr, Kostrzewa, Grażyna, Płoski, Rafał, and Tylki-Szymańska, Anna
- Abstract
Zellweger syndrome (ZS) is a consequence of a peroxisome biogenesis disorder (PBD) caused by the presence of a pathogenic mutation in one of the 13 genes from the PEX family. ZS is a severe multisystem condition characterized by neonatal appearance of symptoms and a shorter life. Here, we report a case of ZS with a mild phenotype, due to a novel PEX6gene mutation. The patient presented subtle craniofacial dysmorphic features and slightly slower psychomotor development. At the age of 2 years, he was diagnosed with adrenal insufficiency, hypoacusis, and general deterioration. Magnetic resonance imaging showed a symmetrical hyperintense signal in the frontal and parietal white matter. Biochemical tests showed elevated liver transaminases, elevated serum very long chain fatty acids, and phytanic acid. After the death of the child at the age of 6 years, molecular diagnostics were continued in order to provide genetic counseling for his parents. Next generation sequencing (NGS) analysis with the TruSight One™ Sequencing Panel revealed a novel homozygous PEX6p.Ala94Pro mutation. In silico prediction of variant severity suggested its possible benign effect. To conclude, in the milder phenotypes, adrenal insufficiency, hypoacusis, and leukodystrophy together seem to be pathognomonic for ZS.
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- 2017
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30. A <italic>de novo</italic> loss‐of‐function <italic>DYNC1H1</italic> mutation in a patient with parkinsonian features and a favourable response to levodopa.
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Szczałuba, K., Rydzanicz, M., Walczak, A., Kosińska, J., Jacoszek, A., Biernacka, A., Gasperowicz, P., Płoski, R., Szymańska, K., Ciara, E., Piekutowska‐Abramczuk, D., Pronicka, E., Czerska, K., and Laure‐Kamionowska, M.
- Subjects
GENETIC mutation ,PARKINSONIAN disorders ,DOPA ,CARBIDOPA ,THERAPEUTICS - Abstract
The article presents a case study of a 20-year-old man with parkinsonism who began to experience neurodevelopmental abnormalities after his first year. It reports about the phenotypes of the loss-of-function de novo mutation of the DYNC1H1 gene. It also states the use and positive response of levodopa-carbidopa for treating the disorders.
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- 2018
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31. The Notch Signalling Pathway in the Development of the Mouse Placenta.
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Gasperowicz, M. and Otto, F.
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PLACENTA diseases ,TROPHOBLAST ,CHORION ,NOTCH genes ,MORPHOGENESIS ,NEOVASCULARIZATION ,LABORATORY mice ,GENETIC mutation ,GENETICS - Abstract
Abstract: Notch signalling is an evolutionarily conserved pathway taking part in many developmental and cell type specification processes. The development of a functional mouse placenta is a dynamic phenomenon involving a number of different processes: trophoblast cell type specification, branching of the chorion and fetal vascular morphogenesis, as well as formation of a maternal blood circulation. In the placenta several members of the Notch signalling pathway and their regulators are expressed. The analysis of mouse strains with targeted mutations in the Notch2, Notch1/4, Hey1/2, Dll4, RBPJκ, and Mash2 genes has demonstrated that these genes are indispensable for a proper placental development. Among them Notch1/4, Hey1/2, Dll4 and RBPJκ have been shown to be crucial for fetal angiogenesis, Notch2 is necessary for formation of maternal blood vessels in the placenta and Mash2 is indispensable for proper trophoblast cell type specification. This review summarizes the current knowledge on the role of the Notch pathway in these various processes happening during placental development. [Copyright &y& Elsevier]
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- 2008
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32. Growth factors and trophoblast differentiation--workshop report.
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Morrish, D.W., Kudo, Y., Caniggia, I., Cross, J., Evain-Brion, D., Gasperowicz, M., Kokozidou, M., Leisser, C., Takahashi, K., and Yoshimatsu, J.
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PROTEIN metabolism ,ANIMALS ,BIOCHEMISTRY ,BLASTOCYST ,CARRIER proteins ,CELL differentiation ,CELL receptors ,CELLULAR signal transduction ,GLYCOPROTEINS ,GROWTH factors ,PHENOMENOLOGY ,MEMBRANE proteins ,MICE ,PLACENTA ,PREECLAMPSIA ,PREGNANCY proteins ,PROTEINS ,TUMOR necrosis factors ,VASCULAR endothelial growth factors - Published
- 2007
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33. Establishing Three Blastocyst Lineages—Then What?
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Gasperowicz, Malgorzata and Natale, David R.C.
- Abstract
Development of the mouse embryo to the blastocyst stage occurs over 3 to 4 days following fertilization of the oocyte. During this time, several molecular and morphological events take place that result in the formation of three distinct cell lineages: the trophectoderm, the epiblast, and the primitive endoderm. Many studies have investigated the processes that control lineage specification in the blastocyst including gene expression, cell signaling, cell–cell contact/positional relationships, and most recently, epigenetics. Here we review, at the molecular level, recent contributions to our understanding of the mechanisms that play a role in formation of these lineages. Additionally, we focus on the next steps in differentiation to highlight processes important in the development of those lineages that contribute to the extraembryonic tissues. In this context, we discuss the establishment of extraembryonic ectoderm and the contributions of parietal and visceral endoderm to yolk sac formation.
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- 2011
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34. Simplified method for gene targeting vector construction
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Gasperowicz, Malgorzata, Kolanczyk, Mateusz, Stock, Michael, and Otto, Florian
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- 2004
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35. Metabolic scaling law for mouse fetal and placental weight.
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Gasperowicz, M., Yampolsky, M., and Salafia, C.M.
- Abstract
Abstract: Human birth weight does not scale linearly with the weight of the placenta: placental mass (PM) is proportional to the fetal mass (FM) raised to the scaling exponent of 0.75 (PM ∼ FM
0.75 ) [1,2]. The mouse is a common model for studying genetic and physiological backgrounds of placental development, function and pathologies. However, to date it has not been known how placental weight scales relative to embryo weight in mice. We analyzed E12.5 litters of CD1 wild-type mice, and found that the mouse placental weight demonstrates a power-law scaling relationship with fetal weight; the value of the scaling exponent is approximately 0.72. [Copyright &y& Elsevier]- Published
- 2013
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36. DNA methylation signature in blood does not predict calendar age in patients with chronic lymphocytic leukemia but may alert to the presence of disease.
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Spólnicka, Magdalena, Zbieć-Piekarska, Renata, Karp, Marta, Machnicki, Marcin M., Własiuk, Paulina, Makowska, Żanetta, Pięta, Agnieszka, Gambin, Tomasz, Gasperowicz, Piotr, Branicki, Wojciech, Giannopoulos, Krzysztof, Stokłosa, Tomasz, and Płoski, Rafał
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DNA methylation ,CHRONIC lymphocytic leukemia ,PATIENTS - Published
- 2018
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37. Vasculogenic mimicry in three-dimensional cultures of murine trophoblast stem cells.
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Rai, Anshita, Gasperowicz, Malgorzata, and Cross, James (Jay)
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- 2013
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38. Placental adaptations in response to protein restricted diet.
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Gasperowicz, Malgorzata, Gonzalez, Paula, Hallgrímsson, Benedikt, and Cross, James
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- 2013
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39. Spatiotemporal expression of Notch receptors and ligands in developing mouse placenta.
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Gasperowicz, Malgorzata, Rai, Anshita, and Cross, James
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- 2013
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40. Establishing Three Blastocyst Lineages—Then What?
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Gasperowicz, Malgorzata and Natale, David R.C.
- Published
- 2010
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41. IFPA Meeting 2011 workshop report II: Angiogenic signaling and regulation of fetal endothelial function; placental and fetal circulation and growth; spiral artery remodeling.
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Bulmer, J.N., Burton, G.J., Collins, S., Cotechini, T., Crocker, I.P., Croy, B.A., Cvitic, S., Desforges, M., Deshpande, R., Gasperowicz, M., Groten, T., Haugen, G., Hiden, U., Host, A.J., Jirkovská, M., Kiserud, T., König, J., Leach, L., Murthi, P., and Pijnenborg, R.
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FETAL development ,CELLULAR signal transduction ,VASCULAR endothelial growth factors ,VENTRICULAR remodeling ,BLOOD circulation ,MEDICAL conferences ,PLACENTA - Abstract
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling. [Copyright &y& Elsevier]
- Published
- 2012
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42. Developmental epileptic encephalopathy in DLG4-related synaptopathy.
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Kassabian B, Levy AM, Gardella E, Aledo-Serrano A, Ananth AL, Brea-Fernández AJ, Caumes R, Chatron N, Dainelli A, De Wachter M, Denommé-Pichon AS, Dye TJ, Fazzi E, Felt R, Fernández-Jaén A, Fernández-Prieto M, Gantz E, Gasperowicz P, Gil-Nagel A, Gómez-Andrés D, Greiner HM, Guerrini R, Haanpää MK, Helin M, Hoyer J, Hurst ACE, Kallish S, Karkare SN, Khan A, Kleinendorst L, Koch J, Kothare SV, Koudijs SM, Lagae L, Lakeman P, Leppig KA, Lesca G, Lopergolo D, Lusk L, Mackenzie A, Mei D, Møller RS, Pereira EM, Platzer K, Quelin C, Revah-Politi A, Rheims S, Rodríguez-Palmero A, Rossi A, Santorelli F, Seinfeld S, Sell E, Stephenson D, Szczaluba K, Trinka E, Umair M, Van Esch H, van Haelst MM, Veenma DCM, Weber S, Weckhuysen S, Zacher P, Tümer Z, and Rubboli G
- Subjects
- Humans, Retrospective Studies, Muscle Hypotonia, Seizures complications, Electroencephalography methods, Disks Large Homolog 4 Protein genetics, Epilepsy diagnostic imaging, Epilepsy genetics, Epilepsy complications, Brain Diseases genetics, Epilepsy, Generalized complications, Intellectual Disability genetics, Intellectual Disability complications
- Abstract
Objective: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy., Methods: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician., Results: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants., Significance: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG., (© 2023 International League Against Epilepsy.)
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- 2024
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43. Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome.
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Misceo D, Senaratne LDS, Mero IL, Sundaram AYM, Bjørnstad PM, Szczałuba K, Gasperowicz P, Kamien B, Nedregaard B, Holmgren A, Strømme P, and Frengen E
- Subjects
- Child, Female, Humans, Infant, Male, Anterior Eye Segment, Mutation, Intestinal Atresia genetics, Microcephaly genetics
- Abstract
Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, we identified novel pathogenic variants in CENPF , including one structural variant, giving a genetic diagnosis to the patients. Patient 1 was a premature baby who died at 26 days with congenital malformations affecting many organs including the brain, eyes, and intestine. She was homozygous for a donor splice variant in CENPF , NM_016343.3:c.1068+1G>A, causing skipping of exon 7, resulting in a frameshift. Patient 2 was a female with intestinal atresia, microcephaly, and a Peters anomaly. She had normal developmental milestones at the age of 7 years. She is compound heterozygous for CENPF NM_016343.3:c.5920dup and c.8991del, both frameshift. Patient 3 was a male with anomalies of the brain, eye, intestine, and kidneys. He was compound heterozygous for CENPF p.(Glu298Ter), and a 5323 bp deletion covering exon 1. CENPF exon 1 is flanked by repetitive sequences that may represent a site of a recurrent structural variation, which should be a focus in patients with Strømme syndrome of unknown etiology.
- Published
- 2023
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44. Epigenetic Findings in Twins with Esophageal Atresia.
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Błoch M, Gasperowicz P, Gerus S, Rasiewicz K, Lebioda A, Skiba P, Płoski R, Patkowski D, Karpiński P, and Śmigiel R
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- Male, Child, Humans, Twins, Monozygotic genetics, Twins, Dizygotic, CpG Islands genetics, Epigenesis, Genetic, Proto-Oncogene Proteins, Guanine Nucleotide Exchange Factors, Rho Guanine Nucleotide Exchange Factors, Esophageal Atresia genetics
- Abstract
Esophageal atresia (EA) is the most common malformation of the upper gastrointestinal tract. The estimated incidence of EA is 1 in 3500 births. EA is more frequently observed in boys and in twins. The exact cause of isolated EA remains unknown; a multifactorial etiology, including epigenetic gene expression modifications, is considered. The study included six pairs of twins (three pairs of monozygotic twins and three pairs of dizygotic twins) in which one child was born with EA as an isolated defect, while the other twin was healthy. DNA samples were obtained from the blood and esophageal tissue of the child with EA as well as from the blood of the healthy twin. The reduced representation bisulfite sequencing (RRBS) technique was employed for a whole-genome methylation analysis. The analyses focused on comparing the CpG island methylation profiles between patients with EA and their healthy siblings. Hypermethylation in the promoters of 219 genes and hypomethylation in the promoters of 78 genes were observed. A pathway enrichment analysis revealed the statistically significant differences in methylation profile of 10 hypermethylated genes in the Rho GTPase pathway, previously undescribed in the field of EA ( ARHGAP36, ARHGAP4, ARHGAP6, ARHGEF6, ARHGEF9, FGD1, GDI1, MCF2, OCRL , and STARD8 ).
- Published
- 2023
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45. Allogenic Adipose-Derived Stem Cells in Diabetic Foot Ulcer Treatment: Clinical Effectiveness, Safety, Survival in the Wound Site, and Proteomic Impact.
- Author
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Mrozikiewicz-Rakowska B, Szabłowska-Gadomska I, Cysewski D, Rudziński S, Płoski R, Gasperowicz P, Konarzewska M, Zieliński J, Mieczkowski M, Sieńko D, Grzela T, Noszczyk M, Paleska B, Czupryniak L, and Lewandowska-Szumiel M
- Subjects
- Animals, Humans, Proteomics, Stem Cells, Adipocytes, Treatment Outcome, Adipose Tissue metabolism, Diabetic Foot therapy, Diabetic Foot metabolism, Diabetes Mellitus metabolism
- Abstract
Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism of action has been studied mainly in vitro and in animals. This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound. Equal groups of 23 participants each received fibrin gel with ADSCs or fibrin gel alone. The clinical effects were assessed at four time points: days 7, 14, 21 and 49. Material collected during debridement from a subset of each group was analyzed for the presence of ADSC donor DNA and proteomic changes. The reduction in wound size was greater at all subsequent visits, significantly on day 21 and 49, and the time to 50% reduction in the wound size was significantly shorter in patients who received ADSCs. Complete healing was achieved at the end of the study in seven patients treated with ADSCs vs. one treated without ADSCs. One week after ADSC application, 34 proteins significantly differentiated the material from both groups, seven of which, i.e., GAPDH, CAT, ACTN1, KRT1, KRT9, SCL4A1, and TPI, positively correlated with the healing rate. We detected ADSC donor DNA up to 21 days after administration. We confirmed ADSC-related improvement in wound healing that correlated with the molecular background, which provides insights into the role of ADSCs in wound healing-a step toward the development of cell-based therapies.
- Published
- 2023
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46. Postzygotic mosaicism of a novel PTPN11 mutation in monozygotic twins discordant for metachondromatosis.
- Author
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Rydzanicz M, Glinkowski W, Walczak A, Koppolu A, Kostrzewa G, Gasperowicz P, Pollak A, Stawiński P, and Płoski R
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- Bone Neoplasms, Chondromatosis, Diseases in Twins diagnosis, Diseases in Twins genetics, Exostoses, Multiple Hereditary, Female, Humans, Mutation, Phenotype, Protein Tyrosine Phosphatase, Non-Receptor Type 11 genetics, Mosaicism, Twins, Monozygotic genetics
- Abstract
Genetic mosaicism caused by postzygotic mutations is of a great interest due to its role in human disease. Monozygotic twins arising from a single zygote are considered as genetically identical, and any differences likely to be caused by postzygotic events. Thus, phenotypically discordant monozygotic twins offer a unique opportunity to study genotype-phenotype correlation. Here, we present a three-generation family starting from a pair of monozygotic twins discordant for metachondromatosis due to postzygotic p.(Gln175His) variant in the PTPN11 gene. Both phenotypically discordant monozygotic twins harbor p.(Gln175His), however significant differences in mosaic ratio is observed not only between twins, but also within different tissue types within one individual. Phenotypic manifestation of p.(Gln175His) in examined family clearly depends on allele variant fraction (VAF). Individuals harboring constitutional mutation (VAF 50%) present typical metachondromatosis. Milder phenotype is observed in twin harboring high-level mosaicism in the tissue of ectodermal origin (VAF 45%), but not in a blood (VAF 5%). Finally, her twin sister harboring low-level mosaicism in blood (VAF 2%) and nonblood (VAF 12%) tissues is phenotypically normal. Our results provide insights into biological role of mosaicism in disease and further support the usefulness of nonblood tissues as an optimal source of DNA for the identification of postzygotic mutations in phenotypically discordant monozygotic twins., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
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47. Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene.
- Author
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Stembalska A, Rydzanicz M, Walas W, Gasperowicz P, Pollak A, Pienkowski VM, Biela M, Klaniewska M, Gamrot Z, Gronska E, Ploski R, and Smigiel R
- Subjects
- Humans, Muscle Hypotonia, Mutation, Nuclear Proteins genetics, Polyneuropathies, Respiratory Distress Syndrome, Newborn, Muscular Atrophy, Spinal genetics, Respiratory Insufficiency genetics
- Abstract
LAS1L encodes a nucleolar ribosomal biogenesis protein and is also a component of the Five Friends of Methylated CHTOP (5FMC) complex. Mutations in the LAS1L gene can be associated with Wilson−Turner syndrome (WTS) and, much more rarely, severe infantile hypotonia with respiratory failure. Here, we present an eighteen-month old boy with a phenotype of spinal muscular atrophy with respiratory distress (SMARD). By applying WES, we identified a novel hemizygous synonymous variant in the LAS1L gene inherited from an unaffected mother (c.846G > C, p.Thr282=). We suggest that the identified variant impairs the RNA splicing process. Furthermore, we proved the absence of any coding regions by qPCR and sequencing cDNA using amplicon deep sequencing and Sanger sequencing methods. According to the SMARD phenotype, severe breathing problems causing respiratory insufficiency, hypotonia, and feeding difficulties were observed in our patient from the first days of life. Remarkably, our case is the second described patient with a SMARD-like phenotype due to a mutation in the LAS1L gene and the first with a variant impacting splicing.
- Published
- 2022
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48. Occurrence of Esophageal Atresia With Tracheoesophageal Fistula in Siblings From Three-Generation Family Affected by Variable Expressivity MYCN Mutation: A Case Report.
- Author
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Klaniewska M, Toczewski K, Rozensztrauch A, Bloch M, Dzielendziak A, Gasperowicz P, Slezak R, Ploski R, Rydzanicz M, Smigiel R, and Patkowski D
- Abstract
The MYCN oncogene encodes a transcription factor belonging to the MYC family. It is primarily expressed in normal developing embryos and is thought to be critical in brain and other neural development. Loss-of-function variants resulting in haploinsufficiency of MYCN , which encodes a protein with a basic helix-loop-helix domain causes Feingold syndrome (OMIM 164280, ORPHA 391641). We present an occurrence of esophageal atresia (EA) with tracheoesophageal fistula in siblings from a three-generation family affected by variable expressivity of MYCN mutation p.(Ser90GlnfsTer176) as a diagnostic effect of searching the cause of familial esophageal atresia using NGS-based whole-exome sequencing (WES). All of our affected patients showed microcephaly and toe syndactyly, which were frequently reported in the literature. Just one patient exhibited clinodactyly. None of the patients exhibited brachymesophalangy or hypoplastic thumbs. The latest report noted that patients with EA and Feingold syndrome were also those with the more complex and severe phenotype. However, following a thorough review of the present literature, the same association was not found, which is also confirmed by the case we described. The variable phenotypic expression of the patients we described and the data from the literature guide a careful differential diagnosis of Feingold syndrome even in cases of poorly expressed and non-specific symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klaniewska, Toczewski, Rozensztrauch, Bloch, Dzielendziak, Gasperowicz, Slezak, Ploski, Rydzanicz, Smigiel and Patkowski.)
- Published
- 2021
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49. A recurrent de novo variant supports KCNC2 involvement in the pathogenesis of developmental and epileptic encephalopathy.
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Rydzanicz M, Zwoliński P, Gasperowicz P, Pollak A, Kostrzewa G, Walczak A, Konarzewska M, and Płoski R
- Subjects
- Brain Diseases physiopathology, Child, Preschool, Developmental Disabilities physiopathology, Epilepsy, Female, Genetic Predisposition to Disease, Humans, Intellectual Disability physiopathology, Mutation, Missense genetics, Phenotype, Exome Sequencing, Brain Diseases genetics, Developmental Disabilities genetics, Intellectual Disability genetics, Shaw Potassium Channels genetics
- Abstract
Developmental and epileptic encephalopathies (DEE) are a heterogenous group of conditions characterized by the co-occurrence of epilepsy and intellectual/developmental disability. Despite several known DEE-related genes, including these encoding ion channels, still many cases remain without molecular diagnosis. Here, we present a 2-year-old girl with severe DEE in whom whole exome sequencing revealed de novo p.(Val471Leu) variant in the KCNC2 encoding Kv3.2, a voltage-gated potassium channel. To the best of our knowledge, this is the third DEE case due to KCNC2 mutation. Our clinical and molecular findings, particularly the recurrence of p.(Val471Leu) in patient with similar clinical phenotype, further support KCNC2 as a novel DEE-associated gene., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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50. Mosaic IL6ST variant inducing constitutive GP130 cytokine receptor signaling as a cause of neonatal onset immunodeficiency with autoinflammation and dysmorphy.
- Author
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Materna-Kiryluk A, Pollak A, Gawalski K, Szczawinska-Poplonyk A, Rydzynska Z, Sosnowska A, Cukrowska B, Gasperowicz P, Konopka E, Pietrucha B, Grzywa TM, Banaszak-Ziemska M, Niedziela M, Skalska-Sadowska J, Stawiński P, Śladowski D, Nowis D, and Ploski R
- Subjects
- Child, Cytokine Receptor gp130 metabolism, Hereditary Autoinflammatory Diseases drug therapy, Hereditary Autoinflammatory Diseases metabolism, Humans, Immunologic Deficiency Syndromes congenital, Immunologic Deficiency Syndromes drug therapy, Immunologic Deficiency Syndromes metabolism, Male, Nitriles pharmacology, Nitriles therapeutic use, Pedigree, Phosphorylation, Piperidines pharmacology, Piperidines therapeutic use, Poland, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Protein Processing, Post-Translational, Pyrazoles pharmacology, Pyrazoles therapeutic use, Pyrimidines pharmacology, Pyrimidines therapeutic use, STAT3 Transcription Factor antagonists & inhibitors, STAT3 Transcription Factor metabolism, White People genetics, Exome Sequencing, Cytokine Receptor gp130 genetics, Hereditary Autoinflammatory Diseases genetics, Immunologic Deficiency Syndromes genetics, Sequence Deletion, Signal Transduction
- Abstract
Interleukin-6 signal transducer (IL6ST) encodes the GP130 protein which transduces the proinflammatory signaling of the IL6 cytokine family through Janus kinase signal transducers and activators of transcription pathway (JAK/STAT) activation. Biallelic loss-of-function IL6ST variants cause autosomal recessive hyper-IgE syndrome or a variant of the Stuve-Wiedemann syndrome. Somatic gain-of-function IL6ST mutations, in particular, small monoallelic in-frame deletions of which the most prevalent is the IL6ST Ser187_Tyr190del, are an established cause of inflammatory hepatocellular tumors, but so far, no disease caused by such mutations present constitutively has been described. Herein, we report a pediatric proband with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphy associated with the IL6ST Tyr186_Tyr190del variant present constitutively. Tyr186_Tyr190del was found by exome sequencing and was shown to be de novo (absent in proband's parents and siblings) and mosaic (present in approximately 15-40% of cells depending on the tissue studied-blood, urine sediment, hair bulbs and buccal swab). Functional studies were performed in the Epstein-Barr virus-immortalized patient's B cell lymphoblastoid cell line, which carried the variant in approximately 95% of the cells. Western blot showed that the patient's cells exhibited constitutive hyperphosphorylation of Tyr705 in STAT3, which is indicative of IL6-independent activation of GP130. Interestingly, the STAT3 phosphorylation could be inhibited with ruxolitinib as well as tofacitinib, which are clinically approved JAK1 and JAK3 (to lesser extent JAK2 and JAK1) inhibitors, respectively. Given our results and the recent reports of ruxolitinib and tofacitinib use for the treatment of diseases caused by direct activation of STAT3 or STAT1, we speculate that these drugs may be effective in the treatment of our patient's condition., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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