Objective： Nance-Horan syndrome （NHS） is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the r...Objective： Nance-Horan syndrome （NHS） is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Methods： Whole exome sequencing analysis was performed on DNA from an affected male to scan for can- didate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. Results： A combi- nation of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G〉T （E108X）in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon （E108X）, resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation （c.322G〉T） occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. Conclusions： We report a nonsense mutation c.322G〉T （E108X） in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis.展开更多
基金supported by the Science and Technology Specific Project of Zhejiang Province(No.2009C03010-2),China
文摘Objective： Nance-Horan syndrome （NHS） is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Methods： Whole exome sequencing analysis was performed on DNA from an affected male to scan for can- didate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. Results： A combi- nation of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G〉T （E108X）in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon （E108X）, resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation （c.322G〉T） occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. Conclusions： We report a nonsense mutation c.322G〉T （E108X） in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis.
