Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

BACKGROUND & OBJECTIVES: Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. METHODS: This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. RESULTS: Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). INTERPRETATION & CONCLUSIONS: Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

Platelet-specific collagen receptor glycoprotein VI gene variants affect recurrent pregnancy loss.

OBJECTIVE: To determine whether platelet-specific collagen receptor glycoprotein VI (GP6) gene variants are associated with recurrent miscarriages (RM). DESIGN: Genetic association study. SETTING: Tertiary care referral hospital. PATIENT(S): A total of 200 women with at least three unexplained spontaneous abortions before 20 weeks of gestation and 300 healthy parous women. INTERVENTION(S): Determination of variants of GP6 single-nucleotide polymorphisms (SNPs) namely; rs1671153, rs1654410, rs1654419, and rs1613662 was based on polymerase chain reaction-restriction fragment-length polymorphism. MAIN OUTCOME MEASURE(S): Genotypes and haplotypes frequencies were compared in RM case subjects versus control subjects. RESULT(S): We observed significantly higher occurrence of rare alleles of SNPs in GP6, namely, rs1671153, rs1654410, rs1654419, and rs1613662, among RM cases, revealing risk association for fetal losses. The synergistic effects of haplotype combinations were also evaluated and showed that four haplotypes G-T-G-G, T-C-A-A, G-C-G-A, and G-T-A-A were more prevalent among RM cases, revealing increased risk for fetal losses. In silico analysis revealed that GP6 has an impact on biologic pathways and significant influence in collagen binding. Gene-gene interaction network analysis revealed that GP6 consisted of a total of 25 interactions with 13 genes in the human genome. CONCLUSION(S): These results suggest that variants of GP6 SNPs, namely, rs1671153, rs1654410, rs1654419, and rs1613662, may be associated with risk of recurrent miscarriage. In silico analyses demonstrated the influence of GP6 in biologic pathways, molecular function, including collagen binding, and gene-gene interaction in the human genome.