Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing.

Abstract

PURPOSE:

Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD.

METHODS:

We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited.

RESULTS:

In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa.

CONCLUSION:

This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD . The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.

• Authors: Xiu-Feng Huang, Fang Huang, Kun-Chao Wu, Juan Wu, Jie Chen, Chi-Pui Pang, Fan Lu, Jia Qu, Zi-Bing Jin
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 17 Issue 4 Pg. 271-8 (Apr 2015) ISSN: 1530-0366 [Electronic] United States
• PMID: 25356976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Aged
• Alleles
• Exome (genetics)
• Female
• Genetic Association Studies
• Genotype
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Mutation, Missense
• Pedigree
• Retinal Dystrophies (diagnosis, genetics, pathology)
• Retinitis Pigmentosa (diagnosis, genetics, pathology)