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Title: Genetics of inherited eye diseases in the Iranian population
Author: Özkan, Ege Gülce
ISNI:       0000 0004 6057 6773
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2016
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Genetic predisposition plays a major role in eye disorders, which could lead to blindness at different stages of life. Identification of novel variants and genes in eye disorders enhances the knowledge and understanding of the molecular pathology of these conditions. Through the GeneSEARCH project, a cohort has been established of consanguineous Iranian families to investigate various syndromic and non-syndromic inherited eye diseases. This specific study focused on 9 of these families presenting with features of Bardet Biedl syndrome, enhanced S- cone syndrome, retinitis pigmentosa, Leber congenital amaurosis, congenital cataract and exophthalmia. The initial ophthalmic examinations and phenotyping were carried out by clinical collaborators in Iran. Linkage analyses and autozygosity mapping were performed to identify the genomic regions most likely to contain the disease-causing gene. Whole exome and Sanger sequencing were performed to detect the causative mutation for each family. This study identifies five novel variants in the following genes: BBS5 (c.382C>G; Bardet Biedl Syndrome); CRB1 (c.361delC; retinitis pigmentosa); GUCY2D (c.2348T>C; Leber congenital amaurosis); FYCO1 (c.l056_1071delGGCCACACGGGACTCA; congenital cataract); and ZBTB11 (c.2708G>A; cataract and mental retardation). In addition, two previously reported variants were also identified in the following genes: NR2E3 (c.932G>A; enhanced S-cone syndrome) and ABCA4 (c.5461-10T>C; retinitis pigmentosa). Two loci associated with exophthalmia and mental retardation, and macular dystrophy were mapped on chromosome 4q24-q27 and chromosomel3ql3.3-ql4.2 respectively. ZBTB11 has not previously been reported as being associated with eye disease. ZBTB11 is thought to encode a transcription factor, but the identified mutation does not alter the functional localization of the protein in the nucleus. It may be possible that this mutation affects the transcriptional activity of the protein. This was supported by microarray analysis indicating reduced expression of BEST1 when comparing mutated ZBTB11 with wild type. Overall, the identification of genes will help the clinical diagnosis, management and genetic counselling in this population, and in the future will open the possibility of specific gene therapy and possible management.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available