Abstract | 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 candidate 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 combination 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.
|
Authors | Nan Hong, Yan-hua Chen, Chen Xie, Bai-sheng Xu, Hui Huang, Xin Li, Yue-qing Yang, Ying-ping Huang, Jian-lian Deng, Ming Qi, Yang-shun Gu |
Journal | Journal of Zhejiang University. Science. B
(J Zhejiang Univ Sci B)
Vol. 15
Issue 8
Pg. 727-34
(Aug 2014)
ISSN: 1862-1783 [Electronic] China |
PMID | 25091991
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Codon, Nonsense
- Membrane Proteins
- NHS protein, human
- Nuclear Proteins
|
Topics |
- Amino Acid Sequence
- Asian People
(genetics)
- Base Sequence
- Cataract
(congenital, genetics)
- China
- Codon, Nonsense
- Conserved Sequence
- DNA Mutational Analysis
- Exons
- Female
- Genetic Diseases, X-Linked
(genetics)
- Heterozygote
- Humans
- Male
- Membrane Proteins
- Molecular Sequence Data
- Mutation
- Nuclear Proteins
(genetics)
- Pedigree
- Phenotype
- Sequence Homology, Amino Acid
- Tooth Abnormalities
(genetics)
|