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Possible dual contribution of a novel GUCY2D mutation in the development of retinal degeneration in a consanguineous population.

Authors
  • Salehi Chaleshtori, Ahmad Reza1
  • Garshasbi, Masoud2
  • Salehi, Ali3
  • Noruzinia, Mehrdad4
  • 1 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. , (Iran)
  • 2 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Iran. , (Iran)
  • 3 Ophthalmology Center, Feiz Hospital, Isfahan University of Medical Sciences, P.O. Box 319, Isfahan, Iran. , (Iran)
  • 4 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Iran. Electronic address: [email protected] , (Iran)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Mar 01, 2020
Volume
63
Issue
3
Pages
103750–103750
Identifiers
DOI: 10.1016/j.ejmg.2019.103750
PMID: 31470097
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Molecular characterization of novel mutations in Leber Congenital Amaurosis (LCA) disease improves the disease diagnosis and contributes to the development of preventive and therapeutic approaches. We studied an isolated inbred population in Iran with a high prevalence of retinal degeneration with clinical variability. The clinical examinations were performed on eight patients belonging to three consanguineous families. The identical-by-descent (IBD) mapping technique was employed to identify the shared loci in patients. Subsequently, Sanger sequencing of the GUCY2D gene, in silico analysis, as well as segregation study were conducted. The whole-exome sequencing method was applied for negative cases of GUCY2D mutation, followed by segregation study in suspected variants among families. A novel deletion mutation in the GUCY2D gene can explain the emergence of LCA-1 in most patients but not all. Besides, a heterozygous variant of uncertain significance (VUS) was observed in the BEST1 gene in some healthy and participant patients. These results further support inter/intra-familial clinical heterogeneity in retinal dystrophy and suggest that screening the GUCY2D gene would be needed for the diagnosis of LCA in Iranian people living in the central regions. The variant in the BEST1 gene might be considered a benign heterozygous variant; however, we hypothesized a possible double heterozygosity in both GUCY2D and BEST1 genes that may cause the pathogenesis of cone-rod dystrophy-6 (CRD-6) disease. This would propose a new scenario for the pathogenesis of a monogenic disorder such as CRD-6 disease in which other genetic elements may be involved in the development of the disease. Copyright © 2019. Published by Elsevier Masson SAS.

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