title: Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes.
abstract: Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
authors.forename: Leen
authors.initials: L
authors.lastname: Abu-Safieh
authors.forename: May
authors.initials: M
authors.lastname: Alrashed
authors.forename: Shamsa
authors.initials: S
authors.lastname: Anazi
authors.forename: Hisham
authors.initials: H
authors.lastname: Alkuraya
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
authors.forename: Jawahir
authors.initials: J
authors.lastname: Al-Zahrani
authors.forename: Lama
authors.initials: L
authors.lastname: Al-Abdi
authors.forename: Mais
authors.initials: M
authors.lastname: Hashem
authors.forename: Salwa
authors.initials: S
authors.lastname: Al-Tarimi
authors.forename: Mohammed-Adeeb
authors.initials: MA
authors.lastname: Sebai
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shamia
authors.forename: Mohamed D
authors.initials: MD
authors.lastname: Ray-Zack
authors.forename: Malik
authors.initials: M
authors.lastname: Nassan
authors.forename: Zuhair N
authors.initials: ZN
authors.lastname: Al-Hassnan
authors.forename: Zuhair
authors.initials: Z
authors.lastname: Rahbeeni
authors.forename: Saad
authors.initials: S
authors.lastname: Waheeb
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alkharashi
authors.forename: Emad
authors.initials: E
authors.lastname: Abboud
authors.forename: Selwa A F
authors.initials: SA
authors.lastname: Al-Hazzaa
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D059472:Exome; D005190:Family; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D058499:Retinal Dystrophies / Q000235:genetics*; D017422:Sequence Analysis, DNA