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Objective: The study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database. Methods: The study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification. Results: The child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-a and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as "Likely pathogenic". Currently, there are no reports in academic literature regarding this specific variant site. Conclusion: LRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities. [ABSTRACT FROM AUTHOR]

Abstract Introduction Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. Methods For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. Results We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. Conclusion In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.

Objective: We present molecular cytogenetic characterization of a de novo chromosome 1q41-q42.11 microdeletion of paternal origin in a mentally retarded child of a family requesting for genetic counseling of the future pregnancy. Case report: A 43-year-old, gravida 1, para 1, woman, who had a 15-year-old son with mental retardation, planned to have another normal child and requested for genetic counseling of the future pregnancy. Her husband was 48 years old. The 15-year-old boy had a body height of 148 cm (

Introduction: Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. Methods: For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. Results: We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. Conclusion: In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos. [ABSTRACT FROM AUTHOR]

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo 3.19-Mb chromosome 14q32.13-q32.2 deletion of paternal origin. Case report: A 36-year-old woman underwent amniocentesis at 20 weeks of gestation because of an advanced maternal age. Her husband was 36 years old. Amniocentesis revealed a karyotype of 46,XY,del(14)(q32.1q32.2). Simultaneous array comparative genomic hybridization (aCGH) analysis showed the result of a 14q32.13-q32.2 deletion. Prenatal ultrasound was unremarkable. The parental karyotypes were normal and did not have such a deletion. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. aCGH was applied on the DNA extracted from cord blood. Polymorphic DNA marker analysis was applied on the DNAs extracted from placenta and parental bloods. aCGH confirmed a 3.19-Mb 14q32.13-q32.2 deletion or arr 14q32.13q32.2 (96,151,751–99,341,476) × 1.0 [GRCh37 (hg19)] encompassing 10 Online Mendelian Inheritance in Man (OMIM) genes of TCL1B, TCL1A, TUNAR, BDKRB2, BDKRB1, ATG2B, GSKIP, AK7, PAPOLA and VRK1. Polymorphic DNA marker analysis confirmed a paternal origin of a de novo interstitial distal 14q deletion. Conclusion: Determination of the paternal origin of a prenatally detected de novo interstitial distal 14q deletion by polymorphic DNA marker analysis in this case is significant, and the information acquired is useful for genetic counseling, especially when amniocentesis is performed because of an advanced maternal age.

Single-copy organelle DNA loci are widely used to infer plants' phylogenetic relationships. In bananas (Musa spp.), the maternal transmission of chloroplast DNA and paternal transmission of mitochondrial DNA provides an excellent possibility to follow both maternal and paternal lineages by using chloroplast and mitochondrial markers, respectively. In the present study, 25 chloroplast and 12 mitochondrial DNA sequences of Musa spp. were used to elucidate the genetic diversity and phylogenetic relationships of wild and cultivated bananas. Sequence alignment and phylogenetic analyses grouped the 34 wild and 26 cultivars into different clades and subclades. The use of cytoplasmic genes to analyze the origin and evolution of cultivated bananas revealed two main maternal and paternal origins: via Musa acuminata Colla and via Musa balbisiana Colla. Relationships among wild accessions and intra- and interspecific hybrids, as well as between the latter, evidenced eight chloroplast and six mitochondrial gene pools, and 18 cytotypes were identified. The maternal origin of most M. acuminata hybrids was the Ca2 gene pool, while the A-B hybrids were derived from the Ca3 or Ca5 gene pools. The most common paternal origin was the Ma3 gene pool, except for ABB genotypes with Mb1 origin. Furthermore, we found a role for Musa itinerans Cheesman in the paternal origin of banana cultivars. The present findings will help refine Musa spp. phylogeny, and enrich the available cytoplasmic data for Musa spp. germplasms that will be useful for improving the breeding of banana cultivars. [ABSTRACT FROM AUTHOR]

Objective: We present detection of paternal origin of fetal trisomy 21 in a pregnancy with isolated ventriculomegaly but without advanced parental age. Case report: A 29-year-old pregnant woman was admitted to the hospital at 18 weeks of gestation for tocolytic treatment because of irregular uterine contractions. Her husband was 30 years old. The couple had a healthy daughter. Prenatal ultrasound incidentally found isolated ventriculomegaly, and subsequent amniocentesis revealed a karyotype of 47,XX,+21 in 20/20 colonies of cultured amniocytes. The pregnancy was terminated, and the fetus manifested characteristic craniofacial appearance of Down syndrome and hyposplastic middle phalanx of the fifth finger. Postnatal polymorphic DNA marker analysis on the DNAs extracted from the cord blood and parental bloods using quantitative fluorescent polymerase chain reaction (QF-PCR) showed a paternal origin of fetal trisomy 21. The father had a karyotype of 46, XY in 40/40 blood lymphocytes. Conclusion: QF-PCR is useful for rapid confirmation of prenatally detected fetal trisomy 21 and determination of paternal origin of fetal trisomy 21 especially in pregnancies with fetal structural abnormalities but without advanced parental age.

Objective: We present detection of paternal origin of fetal trisomy 18 in a pregnancy conceived by assisted reproductive technology (ART) and in vitro fertilization (IVF). Case report: A 39-year-old woman underwent ART and IVF because of primary infertility. The woman was infertile because of myoma and endometriosis. Her husband was 39 years old, and the sperm analysis was normal. The couple was phenotypically normal. This pregnancy was conceived successfully by IVF. She received non-invasive prenatal testing at 11 weeks of gestation, the result showed a high risk for trisomy 18. She underwent chorionic villus sampling at 12 weeks of gestation, and the result was 47,XY,+18 in 24/24 cultured chorionic villi cells. Prenatal ultrasound findings were unremarkable. She underwent amniocentesis at 17 weeks of gestation, and the result was 47,XY,+18 in 20/20 colonies of cultured amniocytes. The pregnancy was subsequently terminated. Postnatal cytogeneic analysis confirmed the prenatal diagnosis. Polymorphic DNA marker analysis on the DNAs extracted from the umbilical cord and parental bloods showed a paternal origin of the extra chromosome 18, indicating a paternal origin of fetal trisomy 18. Cytogenetic analysis of paternal blood revealed a karyotype of 46,XY. Conclusion: Fetal trisomy 18 in pregnancies conceived by ART may be of paternal origin, and determination of paternal origin by polymorphic DNA marker analysis is useful for genetic counseling under such a circumstance.

Abstract Background Migrant women’s overall increased risk of adverse pregnancy outcomes is well known. The aim of this study was to investigate possible associations between stillbirth and maternal country of birth and other migration related factors (paternal origin, reason for immigration, length of residence and birthplace of firstborn child) in migrant women in Norway. Methods Nationwide population-based study including births to primiparous and multiparous migrant women (n = 198,520) and non-migrant women (n = 1,156,444) in Norway between 1990 and 2013. Data from the Medical Birth Registry of Norway and Statistics Norway. Associations were investigated by multiple logistic regression and reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results Primiparous women from Sri-Lanka and Pakistan, and multiparous women from Pakistan, Somalia, the Philippines and Former Yugoslavia had higher odds of stillbirth when compared to non-migrant women (adjusted OR ranged from 1.58 to 1.79 in primiparous and 1.50 to 1.71 in multiparous women). Primiparous migrant women whose babies were registered with Norwegian-born fathers had decreased odds of stillbirth compared to migrant women whose babies were registered with foreign-born fathers (aOR = 0.73; CI 0.58–0.93). Primiparous women migrating for work or education had decreased odds of stillbirth compared to Nordic migrants (aOR = 0.58; CI 0.39–0.88). Multiparous migrant women who had given birth to their first child before arriving in Norway had higher odds of stillbirth in later births in Norway compared with multiparous migrant women who had their first child after arrival (aOR = 1.28; CI 1.06–1.55). Stillbirth was not associated with length of residence in Norway. Conclusions This study identifies sub-groups of migrant women who are at an increased risk of stillbirth, and highlights the need to improve care for them. More attention should be paid to women from certain countries, multiparous women who had their first baby before arrival and primiparous women whose babies have foreign-born fathers.

Objective: the aim of our study was to assess the contribution of quantitative fluorescent polymerase chain reaction (QF-PCR) and pathology studies in the diagnosis of diandric triploidies/partial hydatidiform moles. Methods: this study included all fet al triploidies diagnosed by QF-PCR in chorionic villi or amniotic fluid in the 2 centers of BCNatal in which a maternal saliva sample was used to establish its parental origin. Pathology studies were performed in products of conception and concordance between a partial hydatidiform mole diagnosis and the finding of a diandric triploidy was assessed. Results: among 46 fetal triploidies, found in 13 ongoing pregnancies and in 33 miscarriages, there were 26 (56%) diandric triploidies. Concordant molecular (diandric triploidy) and pathology results (partial mole) were achieved in 14 cases (54%), while in 6 cases (23%) pathology studies were normal, and in the remaining 6 cases (23%) pathology studies could not be performed because miscarriage was managed medically. Conclusions: diandric triploidy is associated with partial hydatidiform mole and its diagnosis is crucial to prevent the development of persistent trophoblastic disease. QF-PCR analysis in chorionic villi or amniotic fluid provides a more accurate diagnosis of the parental origin of triploidy than the classical pathology studies.

Summary: With its vast territory and complex natural environment, China boasts rich cattle genetic resources. To gain the further insight into the genetic diversity and paternal origins of Chinese cattle, we analyzed the polymorphism of Y‐SNPs (UTY19 and ZFY10) and Y‐STRs (INRA189 and BM861) in 34 Chinese cattle breeds/populations, including 606 males representative of 24 cattle breeds/populations collected in this study as well as previously published data for 302 bulls. Combined genotypic data identified 14 Y‐chromosome haplotypes that represented three haplogroups. Y2‐104‐158 and Y2‐102‐158 were the most common taurine haplotypes detected mainly in northern and central China, whereas the indicine haplotype Y3‐88‐156 predominates in southern China. Haplotypes Y2‐108‐158, Y2‐110‐158, Y2‐112‐158 and Y3‐92‐156 were private to Chinese cattle. The population structure revealed by multidimensional scaling analysis differentiated Tibetan cattle from the other three groups of cattle. Analysis of molecular variance showed that the majority of the genetic variation was explained by the genetic differences among groups. Overall, our study indicates that Chinese cattle retain high paternal diversity (H = 0.607 ± 0.016) and probably much of the original lineages that derived from the domestication center in the Near East without strong admixture from commercial cattle carrying Y1 haplotypes. [ABSTRACT FROM AUTHOR]

To further probe into the paternal origins and domestication area of swamp buffaloes, we examined Y‐chromosome diversity of 482 bulls representing 22 populations from China and Southeast Asia. A total of 40 bovine Y‐chromosome‐specific microsatellite (Y‐STR) markers were screened in this study. The results showed that seven Y‐STR markers (UMN2405, UMN0504, UMN0103, UMN1307, BC1.2, UMN0304 and INRA008) were specific and polymorphic in male swamp buffaloes, which can define 9 Y‐haplotypes corresponding to four Y‐haplogroups (Y1, Y2, Y3 and Y4). Haplogroup Y1 was predominant (83.4%) in all swamp buffalo populations, indicating haplogroup Y1 was the major domestication event of swamp buffalo. In addition, the abundant genetic background and backbone of haplogroup Y1 suggested Yangtze Valley as the major domestication area of swamp buffalo. Interestingly, haplogroup Y4 was only confined in Hainan Island which was more ancient than other haplogroups. We hypothesized that haplogroup Y4 was the descendants of the wild Asian buffalo trapped on Hainan Island in prehistoric glacier period and preserved by later introgression into domesticated cows after the domestication. In conclusion, our findings revealed four divergent paternal origins in swamp buffaloes based on Y‐STR markers. [ABSTRACT FROM AUTHOR]

Tetrasomy 14q11q13 is a very rare chromosome aberration. So far, only five patients with such an imbalance were described. All these patients had a de novo marker chromosome idic(14)(q13) leading to a partial tetrasomy of chromosome 14. We report on the first case of a de novo non-mosaic partial tetrasomy 14q resulted not from a marker chromosome, but from an inverted triplication on paternal chromosome 14, characterized by using FISH and SNP array. Our patient showed some anomalies described in tetrasomy 14q11q13 with striking presence of paternal UPD(14) features (blepharophimosis, small thorax, and joint contractures, developmental delay). This unique patient supports the hypothesis that 14q11q13 may contain imprinted gene(s) that contribute to the paternal UPD(14) features of joint contractures and/or blepharophimosis. This patient demonstrates the utility of parent of origin testing in patients with de novo chromosome 14 aberrations. Overdosage of 14q11.1q13.1 may cause some features related to UPD(14) phenotype. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Trisomy 21 Down syndrome is the most common genetic cause for congenital malformations and intellectual disability. It is well known that in the outstanding majority of cases the extra chromosome 21 originates from the mother but only in less than 10 % from the father. The mechanism underlying this striking difference in parental origin of Trisomy 21 Down syndrome is still unknown. However, it seems likely that the main reason is a much higher stringency in the elimination of any trisomy 21 cells during fetal testicular than ovarian development. We have here focussed attention on the paternal gametic output, i.e. the incidence of disomy 21 in spermatozoa. Results: We have used fluorescence in situ hybridisation (FISH) to determine the copy number of chromosome 21 in spermatozoa from 11 men with normal spermiograms. Due to the well-known risk of false positive and false negative signals using a single FISH probe, we have applied two chromosome 21q probes, and we have added a chromosome 18-specific probe to allow differentiation between disomy 21 and diploidy. Analysing a total number of 2000 spermatozoa per case, we documented an average incidence of disomy 21 at 0.13 %, with a range of 0.00-0.25 % and a SD of 0.08. There was no indication of diploidy in this cohort of 22,000 sperm. Conclusion: Numerous previous studies on the incidence of disomy 21 in sperm have been published, using FISH. As far as we are aware, none of these have applied more than a single chromosome 21-specific probe. Accepting our mean of 0.13 % of disomy 21, and providing there is no selective fertilisation capability of disomy 21 sperm in relation to the normal, we conclude that around 1 in 800 conceptions is expected to be trisomic for chromosome 21 of paternal origin. Bearing in mind that the maternal origin likely is at least 10 times more common, we tentatively propose that around 1 in 80 oocytes in the maternal ovarian reserve may be disomy 21. One reason for this discrepancy may be a more stringent selection against aberrant chromosome numbers during spermatogenesis than oogenesis. Further work is required to determine the relevant stages of spermatogenesis at which such a selection may take place. [ABSTRACT FROM AUTHOR]

To determine the Y chromosome genetic diversity and paternal origin of Chinese cattle, 369 bulls from 17 Chinese native cattle breeds and 30 bulls from Holstein and four bulls from Burma were analyzed using a recently discovered USP9Y marker that could distinguish between taurine and indicine cattle more efficiently. In total, the taurine Y1, Y2 haplogroup and indicine Y3 haplogroup were detected in 7 (1.9 %), 193 (52.3 %) and 169 (45.8 %) individuals of 17 Chinese native breeds, respectively, although these frequencies varied amongst the Chinese native cattle breeds examined. Y2 dominates in northern China (91.4 %), while Y3 dominates in southern China (81.2 %). Central China is an admixture zone with Y2 predominating overall (72.0 %). Our results demonstrate that Chinese cattle have two paternal origins, one from B. taurus (Y2) and the other from B. indicus (Y3). The Y1 haplogroup may originate from the imported beef cattle breeds in western countries. The geographical distributions of the Y2 and Y3 haplogroup frequencies reveal a pattern of male indicine introgression from south to north China, and male taurine introgression from north to south China. [ABSTRACT FROM AUTHOR]

Trisomy 21, the cause of Down syndrome (DS), is the most frequent trisomy in humans. The risk for DS increases with maternal age: mothers under 25 years of age are known to have an average risk of a DS pregnancy of 1: 1600, rising to 1: 350 at age 35 and to 1: 40 at 43, respectively. Twins with DS are rare. We report on monozygotic (MZ), monochorionic twin sisters with DS, whose parents are young (24 and 26 years old, respectively) and healthy. Family history is non contributory; pregnancy and delivery were uneventful. Both girls presented at birth with clinical manifestations of Down syndrome, that was confirmed cytogenetically (47XX,+21). Microsatellites analysis indicated that the twins are identical and that the extra chromosome 21 was of paternal origin. Conclusions: For practical purposes, the causative non disjunction should be considered a single sporadic event, with an empirical recurrence risk estimated at about 1%. [ABSTRACT FROM AUTHOR]

We report on a 20-year-old male with severe Charcot–Marie–Tooth (CMT) disease and a de novo deletion (c.281delG, p.G94AfsX17) on the paternal PMP22 allele harboring c.353C>T (p.T118M). RNA-based sequence analysis confirmed the absence of nonsense-mediated decay and the presence of the mutant transcripts in Epstein–Barr virus-transformed lymphoblastoid cells of our patient. His clinical findings included early onset of polyneuropathy, loss of muscle mass with distal pareses, hammer toes, and progressive scoliosis. There was no neuropsychological alteration. Our results suggest that the deletion c.281delG alone is responsible for the severe CMT phenotype. To the best of our knowledge, this is the second report on a proven paternal origin of a de novo single-base mutation in the PMP22 gene. [ABSTRACT FROM AUTHOR]

Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping. Chromosome analysis after amniocentesis revealed a de novo terminal deletion of chromosome 4p [karyotype: 46,XX,del(4) (p16)] which was confirmed by FISH. Analyses of a set of polymorphic markers mapping in 4pter->4p15.3 showed absence of paternal haplotypes. These observations corroborate the preferential paternal origin of the de novo 4p deletion in WHS patients. Furthermore, the distal breakpoint could be narrowed to band 4p16.1. At autopsy, the fetus showed typical craniofacial dysmorphic signs of WHS, severe IUGR and delayed bone age. This report suggests the possibility of recognising the particular phenotype of WHS in utero by prenatal ultrasound and emphasises the importance of karyotyping fetuses with severe IUGR, especially when the amount of amniotic fluid is normal. [ABSTRACT FROM AUTHOR]