A novel duplication involving PRDM13 in a Turkish family supports its role in North Carolina macular dystrophy (NCMD/MCDR1).

Autor:	Small KW; Macula and Retina Institute, Glendale and Los Angeles, CA.; Molecular Insight Research Foundation, Glendale and Los Angeles, CA., Van de Sompele S; Center for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent Belgium., Nuytemans K; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL.; John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL., Vincent A; Ophthalmology, New Zealand National Eye Centre, University of Auckland, New Zealand., Yuregir OO; University of Health Sciences and Adana City Hospital, Adana, Turkey., Ciloglu E; University of Health Sciences and Adana City Hospital, Adana, Turkey., Sariyildiz C; University of Health Sciences and Adana City Hospital, Adana, Turkey., Rosseel T; Center for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent Belgium., Avetisjan J; Macula and Retina Institute, Glendale and Los Angeles, CA.; Molecular Insight Research Foundation, Glendale and Los Angeles, CA., Udar N; Macula and Retina Institute, Glendale and Los Angeles, CA.; Molecular Insight Research Foundation, Glendale and Los Angeles, CA., Vance JM; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL.; John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL., Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL.; John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL., De Baere E; Center for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent Belgium., Shaya FS; Macula and Retina Institute, Glendale and Los Angeles, CA.; Molecular Insight Research Foundation, Glendale and Los Angeles, CA.
Jazyk:	angličtina
Zdroj:	Molecular vision [Mol Vis] 2021 Sep 01; Vol. 27, pp. 518-527. Date of Electronic Publication: 2021 Sep 01 (Print Publication: 2021).
Abstrakt:	Purpose: To clinically and molecularly investigate a new family with North Carolina macular dystrophy (NCMD) from Turkey, a previously unreported geographic origin for this phenotype. Methods: Clinical ophthalmic examinations, including fundus imaging and spectral domain-optical coherence tomography (SD-OCT), were performed on eight members of a two-generation non-consanguineous family from southern Turkey. Whole genome sequencing (WGS) was performed on two affected subjects, followed by variant filtering and copy number variant (CNV) analysis. Junction PCR and Sanger sequencing were used to confirm and characterize the duplication involving PRDM13 at the nucleotide level. The underlying mechanism was assessed with in silico analyses. Results: The proband presented with lifelong bilateral vision impairment and displayed large grade 3 coloboma-like central macular lesions. Five of her six children showed similar macular malformations, consistent with autosomal dominant NCMD. The severity grades in the six affected individuals from two generations are not evenly distributed. CNV analysis of WGS data of the two affected family members, followed by junction PCR and Sanger sequencing, revealed a novel 56.2 kb tandem duplication involving PRDM13 (chr6:99560265-99616492dup, hg38) at the MCDR1 locus. This duplication cosegregates with the NCMD phenotype in the five affected children. No other (likely) pathogenic variants in known inherited retinal disease genes were found in the WGS data. Bioinformatics analyses of the breakpoints suggest a replicative-based repair mechanism underlying the duplication. Conclusions: We report a novel tandem duplication involving the PRDM13 gene in a family with NCMD from a previously unreported geographic region. The duplication size is the smallest that has been reported thus far and may correlate with the particular phenotype. (Copyright © 2021 Molecular Vision.)
Databáze:	MEDLINE
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