NHS gene mutations in non syndromic cataract

Abstract

AbstractPurpose Many genes can be involved in congenital cataracts according to different inheritance pattern. NHS (Nance‐Horan Syndrome) gene is involved in a rare X‐linked syndromic cataract associating dental anomalies and facial dysmorphia. NHS gene mutations are essentially protein truncating mutations. Studies of gene localization show that non‐syndromic form of congenital cataract have a gene located in the same region as the NHS gene. The purpose of this study was to determine if others mutations of the NHS gene might cause non syndromic cataracts and to analyse the expression of NHS in lenses.Methods Genomic DNA was isolated from white blood cells from 30 patients diagnosed with non syndromic congenital cataracts. When a surgery was performed, lenses were collected (n=10). The 11 exons of NHS gene were amplified from genomic DNA by PCR, and the amplicon were directly sequenced. NHS gene copy number anomalies were search by real time PCR. mRNA was extracted from the front capsule of lenses. After reverse transcription mRNA expression was analyzed by real time PCR.Results We identified 6 punctual mutations of NHS gene in different patients : 2 missenses mutations, 3 frameshift mutations and one intronic mutation. The analyze of NHS copy number revealed in one patient a duplication of exons 4 to 8. We manage to extract and amplified NHS mRNA in the front capsule. One patient with a missense mutation has a relative low expression.Conclusion We found 23% mutations of NHS gene in our cohort study. For some patients we can’t yet absolutely eliminate a Nance Horan Syndrom because of their young age. This high rate of mutations mean either the diagnostic of NHS is under evaluate or NHS gene is frequently involved in non syndromic cataracts.