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Background and Objectives : Danon disease is a multisystemic disorder associated with variants in the LAMP2 gene, mainly affecting the cardiac muscle. Here, we report a multigenerational family from Latvia with two male patients, hemizygous for a novel splice-affecting variant c.928+3A>G. Affected patients exhibit a cardiac phenotype, moderate mental disability, and mild retinal changes. Materials and Methods : Both patients underwent either exome or hypertrophic cardiomyopathy gene panel next-generation sequencing. The pathogenic variant effect was determined using reverse transcription, Sanger sequencing, and high-resolution electrophoresis. Results : Evaluation of the splicing process revealed that approximately 80% of the transcripts exhibited a lack of the entire exon 7. This alteration was predicted to cause a shift of the reading frame, consequently introducing a premature stop codon downstream in the sequence. Conclusions : Based on our data, we propose that c.928+3A>G is a pathogenic variant associated with Danon disease.

In this scientometric review, we employ the Web of Science Core Collection to assess current publications and research trends regarding coral reefs in relation to climate change. Thirty-seven keywords for climate change and seven keywords for coral reefs were used in the analysis of 7743 articles on coral reefs and climate change. The field entered an accelerated uptrend phase in 2016, and it is anticipated that this phase will last for the next 5 to 10 years of research publication and citation. The United States and Australia have produced the greatest number of publications in this field. A cluster (i.e., focused issue) analysis showed that coral bleaching dominated the literature from 2000 to 2010, ocean acidification from 2010 to 2020, and sea-level rise, as well as the central Red Sea (Africa/Asia), in 2021. Three different types of keywords appear in the analysis based on which are the (i) most recent (2021), (ii) most influential (highly cited), and (iii) mostly used (frequently used keywords in the article) in the field. The Great Barrier Reef, which is found in the waters of Australia, is thought to be the subject of current coral reef and climate change research. Interestingly, climate-induced temperature changes in "ocean warming" and "sea surface temperature" are the most recent significant and dominant keywords in the coral reef and climate change area.

Mucopolysaccharidosis type I S (MPS IS) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the IDUA gene, leading to a deficiency of the enzyme alpha-L-iduronidase. Enzyme replacement therapy (ERT) reduces lysosomal storage in the liver and improves clinical manifestations. To date, there are no published reports of tuberculosis (TB) treatment in MPS IS patients receiving ERT and as such it is not known whether both conditions can be treated simultaneously. Here, we report the case of a 14-year-old male with MPS IS receiving ERT with laronidase who was diagnosed with a latent TB infection after being in contact with a multi-drug-resistant TB patient. He received prophylactic TB treatment with moxifloxacin for 6 months. No complications were reported and there has been no active TB disease. Our case report demonstrates that TB and MPS IS can be treated simultaneously without serious adverse effects., 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 © 2022 Vasilevska, Kreile, Grinfelde and Skangale.)

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care., (© 2022 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

Background and Objectives: Genetic testing has become an integral part of health care, allowing the confirmation of thousands of hereditary diseases, including neuromuscular disorders (NMDs). The reported average prevalence of individual inherited NMDs is 3.7-4.99 per 10,000. This number varies greatly in the selected populations after applying population-wide studies. The aim of this study was to evaluate the effect of genetic analysis as the first-tier test in patients with NMD and to calculate the disease prevalence and allelic frequencies for reoccurring genetic variants., Methods: Patients with NMD from Latvia with molecular tests confirming their diagnosis in 2008-2020 were included in this retrospective study., Results: Diagnosis was confirmed in 153 unique cases of all persons tested. Next-generation sequencing resulted in a detection rate of 37%. Two of the most common childhood-onset NMDs in our population were spinal muscular atrophy and dystrophinopathies, with a birth prevalence of 1.01 per 10,000 newborns and 2.08 per 10,000 (male newborn population), respectively. The calculated point prevalence was 0.079 per 10,000 for facioscapulohumeral muscular dystrophy type 1, 0.078 per 10,000 for limb-girdle muscular dystrophy, 0.073 per 10,000 for nondystrophic congenital myotonia, 0.052 per 10,000 for spinobulbar muscular atrophy, and 0.047 per 10,000 for type 1 myotonic dystrophy., Discussion: DNA diagnostics is a successful approach. The carrier frequencies of the common CAPN3 , FKRP , SPG11 , and HINT1 gene variants as well as that of the SMN1 gene exon 7 deletion in the population of Latvia are comparable with data from Europe. The carrier frequency of the CLCN1 gene variant c.2680C>T p.(Arg894Ter) is 2.11%, and consequently, congenital myotonia is the most frequent NMD in our population., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Craniofacial morphogenesis is highly complex, as is the anatomical region involved. Errors during this process, resulting in orofacial clefts, occur in more than 400 genetic syndromes. Some cases of cleft lip and/or palate (CLP) are caused by mutations in single genes; however, complex interactions between genetic and environmental factors are considered to be responsible for the majority of non-syndromic CLP development. The aim of the current study was to identify genetic risk factors in patients with isolated cleft palate (CP) by whole genome sequencing. Patients with isolated CP ( n = 30) recruited from the Riga Cleft Lip and Palate Centre, Institute of Stomatology, Riga, were analyzed by whole genome sequencing. Pathogenic or likely pathogenic variants were discovered in genes associated with CP ( TBX22 , COL2A1 , FBN1 , PCGF2 , and KMT2D ) in five patients; hence, rare disease variants were identified in 17% of patients with non-syndromic isolated CP. Our results were relevant to routine genetic counselling practice and genetic testing recommendations. Based on our data, we propose that all newborns with orofacial clefts should be offered genetic testing, at least for a panel of known CLP genes. Only if the results are negative and there is no suggestive family history or additional clinical symptoms (which would support additional exome or genome-wide investigation), should multifactorial empiric recurrence risk prediction tools be applied for families., 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 © 2022 Lace, Pajusalu, Livcane, Grinfelde, Akota, Mauliņa, Barkāne, Stavusis and Inashkina.)

Leigh syndrome is a neurodegenerative disorder with an incidence of 1 : 40,000 live births. The clinical presentation of LS is highly variable with heterogeneity in the disease-associated symptoms of cerebellar, motor, and extrapyramidal dysfunction and common infections. There is no effective treatment for this condition; as such, the prognosis of this condition is very poor with death occurring within the first few years of life. In this study, we report the first LS case in Latvia with SURF1 pathogenic variants in two siblings. The difficulties encountered establishing a diagnosis for the first proband and the effective prenatal diagnosis for the second offspring that led to termination of the pregnancy are discussed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Arta Katkevica et al.)

Hereditary ectodermal dysplasias are a complex group of inherited disorders characterised by abnormalities in two or more ectodermal derivatives (skin, nails, sweat glands, etc. ). There are two main types of these disorders - hidrotic and hypohidrotic/anhidrotic ectodermal dysplasias. Hypohidrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome (OMIM: 305100) occurs in 1 out of 5000-10,000 births [19] and has an X-linked recessive inheritance pattern (X-linked hypohydrotic ectodermal dysplasia - XLHED) [2]. The main cause of XLHED is a broad range of pathogenic variants in the EDA gene (HGNC:3157, Xq12-13) which encodes the transmembrane protein ectodysplasin-A [4]. We report here the case of a patient with a novel inherited allelic variant in the EDA gene - NM_001399.5:c.337C>T (p.Gln113*) - in the heterozygous state. Targeted family member screening was conducted and other carriers of this EDA gene pathogenic variant were identified and phenotypically characterised. The patient subsequently underwent in vitro fertilisation with preimplantation genetic testing for monogenic diseases (PGT-M)., (© 2021 The Authors.)

The data set provided in this article consist of two repeated data sets of chemical elements concentrations in snow samples. The snow samples were collected in Jelgava city at December 15th with 5 day exposition time. Snow samples were collected in 59 monitoring points in Jelgava city and in one sample in rural area monitoring point as control. The collected snow samples were melted, acidified with HNO 3 and analysed with ICP-MS. The samples were analysed Aluminium (Al), Silicon (Si), Chrome (Cr), Manganese (Mn), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Arsenic (As), Molybdenum (Mo), Cadmium (Cd), Barium (Ba), Tungsten (W), Lead (Pb). The collected data are with fundamental scientific value and can be applied only for local data analysis. Data set is useful for local city air quality research work and for evaluation not only local urban impact but in future evaluate city green infrastructure impact on air quality and evaluation of air pollution mitigation measures efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 The Author(s).)

Aim: The aim of this study is to summarize the outcomes of transfers of mosaic embryos, which were classified according to guidelines and in strong collaboration of reproductologists, clinical geneticists and patients approved as suitable for transfer. Material and Methods: Retrospective data were collected from 70 patients from a private IVF center to whom embryos with mosaic changes in chromosomal material were transferred from 2015 to 2019. Results and Conclusion: Implantation outcomes and continuing pregnancies showed slight differences, when compared to fully normal embryos. Artifacts have to be differentiated from undeniable aberrations, and correct interpretation of results must be done with following patient counselling and prenatal testing if necessary.

Male factor infertility accounts for 40-50% of all infertility cases. Deletions of one or more AZF region parts in chromosome Y are one of the most common genetic causes of male infertility. Usually full or partial AZF deletions, including genes involved in spermatogenesis, are associated with spermatogenic failure. Here we report a case of a Caucasian man with partial AZFa region deletion from a couple with secondary infertility. Partial AZFa deletion, involving part of USP9Y gene appears to be benign, as we proved transmission from father to son. According to our results, it is recommended to revise guidelines on markers selected for testing of AZFa region deletion, to be more selective against DDX3Y gene and exclude probably benign microdeletions involving only USP9Y gene., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Baiba Alksere et al.)

Aim: The aim of the research was to evaluate the growth performance, to measure the amount of methane (CH 4 ) and carbon dioxide (CO 2 ) in calves' rumen, and to compare the obtained results between the control group (CoG) and the experimental group (Pre12) which received the additional supplement of the prebiotic inulin., Materials and Methods: The research was conducted with ten Holstein Friesian ( Bos taurus L.) crossbreed calves with an average age of 33±6 days. Calves were split into two groups: 5 calves that were fed with the control non-supplemented diet (CoG) and 5 calves that were fed with the same diet further supplemented with 12 g of flour of Jerusalem artichoke ( Helianthus tuberosus L.) containing 6 g of prebiotic inulin per 0.5 kg of barley flour diet (Pre12). The duration of the experiment was 56 days. CH 4 and CO 2 were measured using cavity ringdown spectroscopy device Picarro G2508. The weight and samples from calves' rumen were evaluated 3 times during the experimental period - on the 1 st , 28 th , and 56 th days. Samples were obtained by puncturing the calf rumen., Results: The weight gain (kg) during the whole experimental period was higher in the Pre12 (65.8±6.57) compared to CoG (36.8±7.98) calves (p<0.001). The daily weight gain was also increased in the Pre12 (1.2±0.12) than CoG (0.7±0.14) calves (p<0.001). There was no difference in the levels of CH 4 and CO 2 produced in the rumen of CoG and Pre12 calves (p>0.05)., Conclusion: The main results showed that the prebiotic inulin can promote weight gain in calves, without affecting the mean concentration of CH 4 and CO 2 in calves' rumen.

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8 ± 6.2 (11-39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3 ± 2.4 (11-22) gestational weeks, and the mean gestational age at termination was 19.3 ± 4.1 (13-26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Cleft lip (CL) with or without palate (CLP) and isolated cleft palate (CP) are etiologically complex diseases with interactions among various environmental and genetic factors. The aim of the current study was to identify association with genetic markers and phenotypic craniofacial data in patients with CL/CLP/CP parents., Methods: Posteroanterior and lateral digital radiographs of the cranium were obtained from 74 parents of patients with CL/CLP/CP. One hundred seventy-three patients with CL/CLP/CP and 190 controls were enrolled in the study for the association test. Five genetic markers of the IRF6 gene and 14 markers of the 19q13 locus were genotyped. Linear regression analysis was performed for the relationship of cephalometric measurements with genotype data adjusted for age, gender, and cleft type. Chi-square and transmission disequilibrium tests were performed to evaluate differences in alleles of the BCL3 gene. Positive findings were replicated in an independent sample (n = 95) of patients with CL/CLP/CP parents., Results: Genetic markers of the BCL3 gene at 19q13, rs7257231, and rs1979377 in the familial association test and rs10401176 in the case-control association test, were associated with craniofacial phenotype. Carriers of BCL3 allele rs7257231T had longer posterior cranial bases than noncarriers (p(adjusted) = 0.0028), and in the familial-based association test showed the statistically strongest relationship (p(adjusted) = 0.05) to phenotype. Relation of rs7257231 to facial formation was confirmed in the replication group (p = 0.0024)., Conclusions: The results indicate that BCL3, which has functions related to cell adhesion and whose downregulation can cause disruption of ectodermal development, is likely to be important in facial formation. Birth Defects Research (Part A), 2012., (Copyright © 2012 Wiley Periodicals, Inc.)

Isolated cleft lip and/or palate (CL/CLP) is a complex congenital anomaly with many contributing factors. There are several genes involved in the aetiology of CL/CLP, they are different in selected populations. In a previous study, the mitochondrial haplotypes of Latvian subjects with CL/CLP were characterized. Latvian subjects with CL/CLP have mostly mitochondrial haplogroups U4/U5 compared with the ethnic population of Latvia. The aim of this study was to stratify the results of genotyping based on European mitochondrial DNA (mtDNA) haplotypes. DNA samples from 108 patients with CL/CLP and from 182 unrelated and unaffected individuals selected randomly in Latvia (used as controls) were obtained for investigation. In this study, we analysed the data taking into consideration mitochondrial haplogroups and found that gene associations depended on the genetic origin of the population. The phenotype of patients with non-U haplotypes was associated with markers in wingless-type MMTV integration site family, member 3 (WNT3), collagen, type XI, alpha 2 (COL11A2), and fibroblast growth factor receptor 1 (FGFR1), whereas patients with U4 and U5 haplotypes showed significant association with WNT3 and COL11A2. It is unlikely that mtDNA variants play a direct role in the development of CL/CLP; rather, they may be a surrogate for population substructure and provide a tool to increase homogeneity and statistical power., (© 2011 Eur J Oral Sci.)

Unlabelled: Human Y chromosome is used as a tool in male infertility and population genetic studies. The aims of this research were to analyse the prevalence of Y chromosome microdeletions among infertile Latvian men, and to identify possible lineages of Y chromosome that may be at increased risk of developing infertility. A study encompassed 105 infertile men with different spermatogenic disturbances. Deletions on Y chromosome were detected in 5 out of 105 (approximately 5%) cases analysed in this study. Three of them carried deletion in AZFc region and two individuals had AZFa + b + c deletion. Study of Y chromosome haplogroups showed that N3a1 and R1a1 lineages were found less frequently in the infertile male group compared to ethnic Latvian group, however K* cluster was predominantly found in infertile male Y chromosomes., Conclusions: 1) Our study advocates running Y chromosome microdeletion analyses only in cases of severe form of infertility; 2) Y chromosome haplogroup analysis showed statistically significant tendencies that some haplogroups are more common in ethnic male group, but others are more common in infertile males.