TY - JOUR
T1 - Whole exome sequencing reveals GUCY2D as a major gene associated with cone and cone–rod dystrophy in Israel
AU - Lazar, Csilla H.
AU - Mutsuddi, Mousumi
AU - Kimchi, Adva
AU - Zelinger, Lina
AU - Mizrahi-Meissonnier, Liliana
AU - Marks-Ohana, Devorah
AU - Boleda, Alexis
AU - Ratnapriya, Rinki
AU - Sharon, Dror
AU - Swaroop, Anand
AU - Banin, Eyal
N1 - Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2015/11/30
Y1 - 2015/11/30
N2 - Methods. Clinical analysis included family history, detailed ocular examination, visual function testing, and retinal imaging. Whole exome sequencing, followed by segregation analysis, was performed in 6 cone-dominated retinopathy families in which prior mutation analysis did not reveal the causative gene. Based on the WES findings, we screened 106 additional families with cone-dominated phenotypes.Results. The WES analysis revealed mutations in known retinopathy genes in five of the six families: two pathogenic mutations in the GUCY2D gene in three families, and one each in CDHR1 and C8orf37. Targeted screening of additional cone-dominated families led to identification of GUCY2D mutations in four other families, which included two highly probable novel disease-causing variants.Conclusions:. Our study suggested that GUCY2D is a major cause of autosomal dominant cone and cone–rod dystrophies in Israel; this is similar to other Caucasian populations and is in contrast with retinitis pigmentosa (primary rod disease), where the genetic make-up of the Israeli population is distinct from other ethnic groups. We also conclude that WES permits more comprehensive and rapid analyses that can be followed by targeted screens of larger samples to delineate the genetic structure of retinal disease in unique population cohorts.Purpose. The Israeli population has a unique genetic make-up, with a high prevalence of consanguineous marriages and autosomal recessive diseases. In rod-dominated phenotypes, disease-causing genes and mutations that differ from those identified in other populations often are incurred. We used whole exome sequencing (WES) to identify genetic defects in Israeli families with cone-dominated retinal phenotypes.
AB - Methods. Clinical analysis included family history, detailed ocular examination, visual function testing, and retinal imaging. Whole exome sequencing, followed by segregation analysis, was performed in 6 cone-dominated retinopathy families in which prior mutation analysis did not reveal the causative gene. Based on the WES findings, we screened 106 additional families with cone-dominated phenotypes.Results. The WES analysis revealed mutations in known retinopathy genes in five of the six families: two pathogenic mutations in the GUCY2D gene in three families, and one each in CDHR1 and C8orf37. Targeted screening of additional cone-dominated families led to identification of GUCY2D mutations in four other families, which included two highly probable novel disease-causing variants.Conclusions:. Our study suggested that GUCY2D is a major cause of autosomal dominant cone and cone–rod dystrophies in Israel; this is similar to other Caucasian populations and is in contrast with retinitis pigmentosa (primary rod disease), where the genetic make-up of the Israeli population is distinct from other ethnic groups. We also conclude that WES permits more comprehensive and rapid analyses that can be followed by targeted screens of larger samples to delineate the genetic structure of retinal disease in unique population cohorts.Purpose. The Israeli population has a unique genetic make-up, with a high prevalence of consanguineous marriages and autosomal recessive diseases. In rod-dominated phenotypes, disease-causing genes and mutations that differ from those identified in other populations often are incurred. We used whole exome sequencing (WES) to identify genetic defects in Israeli families with cone-dominated retinal phenotypes.
KW - Inherited blindness
KW - Next generation sequencing
KW - Photoreceptor degeneration
UR - http://www.scopus.com/inward/record.url?scp=84921453156&partnerID=8YFLogxK
U2 - 10.1167/iovs.14-15647
DO - 10.1167/iovs.14-15647
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C2 - 25515582
AN - SCOPUS:84921453156
SN - 0146-0404
VL - 56
SP - 420
EP - 430
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 1
ER -