Expanding the Clinical, Allelic, and Locus Heterogeneity of Retinal Dystrophies

Overview

Journal Genet Med

Publisher Elsevier

Specialty Genetics

Date 2015 Sep 11

PMID 26355662

Citations 55

Authors

Nisha Patel

Mohammed A Aldahmesh

Hisham Alkuraya

Shamsa Anazi

Hadeel Alsharif

Arif O Khan

Asma Sunker

Saleh Al-Mohsen

Emad B Abboud

Sawsan R Nowilaty

Mohammed Alowain

Hamad Al-Zaidan

Bandar Al-Saud

Ali Alasmari

Ghada M H Abdel-Salam

Mohamed Abouelhoda

Firdous M Abdulwahab

Niema Ibrahim

Ewa Naim

Banan Al-Younes

Abeer E AlMostafa

Abdulelah Alissa

Mais Hashem

Olga Buzovetsky

Yong Xiong

Dorota Monies

Nada AlTassan

Ranad Shaheen

Selwa A F Al-Hazzaa

Fowzan S Alkuraya

Affiliations

Soon will be listed here.

Abstract

Purpose: Retinal dystrophies (RD) are heterogeneous hereditary disorders of the retina that are usually progressive in nature. The aim of this study was to clinically and molecularly characterize a large cohort of RD patients.

Methods: We have developed a next-generation sequencing assay that allows known RD genes to be sequenced simultaneously. We also performed mapping studies and exome sequencing on familial and on syndromic RD patients who tested negative on the panel.

Results: Our panel identified the likely causal mutation in >60% of the 292 RD families tested. Mapping studies on all 162 familial RD patients who tested negative on the panel identified two novel disease loci on Chr2:25,550,180-28,794,007 and Chr16:59,225,000-72,511,000. Whole-exome sequencing revealed the likely candidate as AGBL5 and CDH16, respectively. We also performed exome sequencing on negative syndromic RD cases and identified a novel homozygous truncating mutation in GNS in a family with the novel combination of mucopolysaccharidosis and RD. Moreover, we identified a homozygous truncating mutation in DNAJC17 in a family with an apparently novel syndrome of retinitis pigmentosa and hypogammaglobulinemia.

Conclusion: Our study expands the clinical and allelic spectrum of known RD genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates.Genet Med 18 6, 554-562.

Citing Articles

Genetics and diagnostics of inherited retinal diseases in the era of whole genome sequencing.

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Expanding the Mutation Spectrum for Inherited Retinal Diseases.

Lynn J, Huang S, Trigler G, Kingsley R, Coussa R, Bennett L Genes (Basel). 2025; 16(1).

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Variants in the AGBL5 gene are responsible for autosomal recessive Retinitis pigmentosa with hearing loss.

Karali M, Garcia-Garcia G, Kaminska K, AlTalbishi A, Cancellieri F, Testa F Eur J Hum Genet. 2024; .

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Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration.

Sangermano R, Gupta P, Price C, Han J, Navarro J, Condroyer C NPJ Genom Med. 2024; 9(1):58.

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