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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 (

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.

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.

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.

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. Electronic supplementary material The online version of this article (10.1186/s12884-018-2140-3) contains supplementary material, which is available to authorized users.

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.

Spinal muscular atrophy (SMA) is a relatively common autosomal recessive neuromuscular disorder. We have identified de novo rearrangements in 7 (approximately 2%) index patients from 340 informative SMA families. In each, the rearrangements resulted in the absence of the telomeric copy of the survival motor neuron (SMN) gene (telSMN), in two cases accompanied by the loss of the neuronal apoptosis-inhibitory protein gene . Haplotype analysis revealed unequal recombination in four cases, with loss of markers Ag1-CA and C212, which are near the 5' ends of the SMN genes. In one case, an interchromosomal rearrangement involving both the SMN genes and a regrouping of Ag1-CA and C212 alleles must have occurred, suggesting either interchromosomal gene conversion or double recombination. In two cases, no such rearrangement was observed, but loss of telSMN plus Ag1-CA and C212 alleles in one case suggested intrachromosomal deletion or gene conversion. In six of the seven cases, the de novo rearrangement had occurred during paternal meiosis. Direct detection of de novo SMA mutations by molecular genetic means has allowed us to estimate for the first time the mutation rate for a recessive disorder in humans. The sex-averaged rate of 1.1 x 10(-4), arrived at in a proband-based approach, compares well with the rate of 0.9 x 10(-4) expected under a mutation-selection equilibrium for SMA. These findings have important implications for genetic counseling and prenatal diagnosis in that they emphasize the relevance of indirect genotype analysis in combination with direct SMN-gene deletion testing in SMA families.

Summary Between April 1991 and December 1994, epidemiological studies detected a population with a high prevalence of Down syndrome in El Valles, Spain. Parallel double studies were carried out to determine the parental and the meiotic origins of the trisomy 21, by use of DNA polymorphisms, and to establish the incidence of disomy 21 in the spermatozoa of the fathers of affected children, by use of multicolor FISH. Results show that the overall incidence of chromosome 21 disomy in the fathers of affected children was not significantly different from that in the control population (0.31% vs. 0.37%). However, analysis of individual data demonstrates that two cases (DP-4 and DP-5) with significant increases of disomy 21 (0.75% and 0.78% vs. 0.37%) correspond to the fathers of the two individuals with Down syndrome of paternal origin. DP-5 also had a significant increase of sex-chromosome disomies (0.69% vs. 0.37%) and of diploid spermatozoa (1.13% vs. 0.24%).