Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature.

PURPOSE: Congenital hereditary endothelial dystrophy 2 (CHED2) is an autosomal recessive disorder caused by mutations in the solute carrier family 4, sodium borate transporter, member 11 (SLC4A11) gene. The purpose of this study was to identify the genetic cause of CHED2 in six Indian families and catalog all known mutations in the SLC4A11 gene. METHODS: Peripheral blood samples were collected from individuals of the families with CHED2 and used in genomic DNA isolation. PCR primers were used to amplify the entire coding region including intron-exon junctions of SLC4A11. Amplicons were subsequently sequenced to identify the mutations. RESULTS: DNA sequence analysis of the six families identified four novel (viz., p.Thr262Ile, p.Gly417Arg, p.Cys611Arg, and p.His724Asp) mutations and one known p.Arg869His homozygous mutation in the SLC4A11 gene. The mutation p.Gly417Arg was identified in two families. CONCLUSIONS: This study increases the mutation spectrum of the SLC4A11 gene. A review of the literature showed that the total number of mutations in the SLC4A11 gene described to date is 78. Most of the mutations are missense, followed by insertions-deletions. The present study will be helpful in genetic diagnosis of the families reported here.

Superior Vena Cava Resection in Locally Advanced Thymoma-Surgical and Survival Outcomes.

This study was aimed at reporting the surgical management of superior vena cava invasion in patients with locally advanced thymoma and to evaluate surgical and survival outcomes. This is a retrospective analysis of 12 patients operated for superior vena cava resection for locally advanced thymoma over 8 years in a thoracic surgery centre in India. An analysis of peri-operative variables including complications was carried out. The influence of various predictors on survival was assessed by log-rank test. Intra-operatively, superior vena cava (SVC) alone was involved in 3 (25%) cases, SVC with BCV involvement was there in 8 cases (66.7%) and in 1 patient, the SVC involvement extended into the right atrium also. In all cases, the tumour was resected en bloc with the involved part of SVC. Repair with primary closure was sufficient in 2 cases (16.6%) in view of < 1/3rd of circumferential involvement. However, in remaining 10 cases, SVC was replaced with PTFE graft (single graft in 6 cases, Y-graft in 2 cases and twin grafts in 2 cases). No peri-operative deaths. Overall survival (OS) at 1, 3 and 5 years was 100%, 91.6% and 83.3%, respectively. Myasthenia gravis and higher Masaoka stage (IV A) of the disease were poor predictors of survival. Superior vena cava resection and reconstruction is a feasible and oncologically superior option in invasive thymoma with SVC involvement. This challenging surgical procedure should only be attempted by an experienced team of thoracic and cardiac surgeons at high-volume centre to achieve best outcomes.