Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder.

Breast augmentation has been increasing steadily in popularity over the past three decades. Many of these patients present with secondary problems or complications following their primary breast augmentation. Two of the most common complications are capsular contracture and implant malposition. Familiarity and comfort with the assessment and management of these complications is necessary for all plastic surgeons. An up-to-date understanding of current devices and techniques may decrease the need to manage future complications from the current cohort of breast augmentation patients.

FVL mutation is more common in North Indians than previously believed and it predisposes the women to PE. MTHFR mutant allele is paradoxically protective. ACE polymorphism appears to predispose to severe PE but not nonsevere PE. No significant contribution of AGT polymorphism to PE is found.

The association of four common polymorphisms of vascular endothelial growth factors (VEGF) with recurrent miscarriages(RM) was evaluated in North Indian women for 200 patients with RM and 200 controls. The subjects were genotyped for the polymorphisms 2578C/A, 2549 18-bp I/D, 1154G/A and +936C/T. Association of VEGF genotypes, alleles and haplotypes with recurrent miscarriage were evaluated by Fisher’s exact test. 1154G/A and +936C/T modified the risk of RM. The 1154A allel and +936T allel significantly increased the risk of RM (OR = 1.485, P = 0.0210, 95% CI 1.072–2.057 and OR = 1.869, P = 0.0054, 95% CI 1.214–2.876 respectively). Risk was further increased when –1154A/A genotype and +936C/T genotype were considered (OR = 2.0, P = 0.0310,95% CI 1.068–3.747 and OR = 1.716, P = 0.0293, 95% CI 1.058–2.784 respectively). However, no association was found between 2578C/A or 2549 18-bp I/D and RM. Four haplotypes, AIAC, ADAC, CIAT and ADGT, were found to predispose to RM while the haplotypes CIAC, CDGT and ADGC were found to show protective effect. In conclusion, two common polymorphisms of the VEGF gene,1154G/A and +936C/T, increase the risk of RM in North Indian women. RM is also predisposed in the presence of haplotypes AIAC,ADAC, CIAT and ADGT.

Objective: To ascertain the performance of exome sequencing (ES) technology for determining the etiological basis of abnormal perinatal phenotypes and to study the impact of comprehensive phenotyping on variant prioritization. Methods: A carefully selected cohort of 32/204 fetuses with abnormal perinatal phenotypes following postmortem/postnatal deep phenotyping underwent ES to identify a causative variant for the fetal phenotype. A retrospective comparative analysis of the prenatal versus postmortem/postnatal phenotype-based variant prioritization was performed with aid of Phenolyzer software. A review of selected literature reports was done to examine the completeness of phenotypic information for cases in those reports and how it impacted the performance of fetal ES. Results: In 18/32 (56%) fetuses, a pathogenic/likely pathogenic variant was identified. This included novel genotype-phenotype associations, expanded prenatal phenotypes of known Mendelian disorders and dual Mendelian diagnoses. The retrospective analysis revealed that the putative diagnostic variant could not be identified on basis of prenatal findings alone in 15/22 (68%) cases, indicating the importance of comprehensive postmortem/postnatal phenotype information. Literature review was supportive of these findings but could not be conclusive due to marked heterogeneity of involved studies. Conclusion: Comprehensive phenotyping is essential for improving diagnostic performance and facilitating identification of novel genotype-phenotype associations in perinatal cohorts undergoing ES.