Distinct mutations with different inheritance mode caused similar retinal dystrophies in one family: a demonstration of the importance of genetic annotations in complicated pedigrees

Journal of Translational Medicine
Xue ChenChen Zhao

Abstract

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy presenting remarkable genetic heterogeneity. Genetic annotations would help with better clinical assessments and benefit gene therapy, and therefore should be recommended for RP patients. This report reveals the disease causing mutations in two RP pedigrees with confusing inheritance patterns using whole exome sequencing (WES). Twenty-five participants including eight patients from two families were recruited and received comprehensive ophthalmic evaluations. WES was applied for mutation identification. Bioinformatics annotations, intrafamilial co-segregation tests, and in silico analyses were subsequently conducted for mutation verification. All patients were clinically diagnosed with RP. The first family included two siblings born to parents with consanguineous marriage; however, no potential pathogenic variant was found shared by both patients. Further analysis revealed that the female patient carried a recurrent homozygous C8ORF37 p.W185*, while the male patient had hemizygous OFD1 p.T120A. The second family was found to segregate mutations in two genes, TULP1 and RP1. Two patients born to consanguineous marriage carried homozygous TULP1 p.R419...Continue Reading

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Citations

Sep 9, 2020·Biochemical Society Transactions·Manuela Morleo, Brunella Franco
Feb 4, 2022·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Nunziana PezzellaBrunella Franco

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Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

PyMol
PolyPhen
PolyPhen PROVEN
SNP2
MODEL
gnomAD
Indel2
SWISS
CASAVA
Atlas

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