학술논문
Identification of a novel large multigene deletion and a frameshift indel in PDE6B as the underlying cause of early-onset recessive rod-cone degeneration.
Document Type
Academic Journal
Author
Sangermano R; Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.; Biswas P; Shiley Eye Institute, University of California San Diego, La Jolla, California 92093, USA.; Sullivan LS; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.; Place EM; Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.; Borooah S; Shiley Eye Institute, University of California San Diego, La Jolla, California 92093, USA.; Straubhaar J; Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.; Pierce EA; Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.; Daiger SP; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.; Bujakowska KM; Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.; Ayaggari R; Shiley Eye Institute, University of California San Diego, La Jolla, California 92093, USA.
Source
Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 101660017 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2373-2873 (Electronic) Linking ISSN: 23732873 NLM ISO Abbreviation: Cold Spring Harb Mol Case Stud Subsets: MEDLINE
Subject
Language
English
Abstract
A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the PDE6B gene in the affected twins and their unaffected father. Further investigation, using genome sequencing, identified a novel ∼7.5-kb deletion (Chr 4:670,405-677,862del) encompassing the ATP5ME gene, part of the 5' UTR of MYL5 , and a 378-bp (Chr 4:670,405-670,782) region from the 3' UTR of PDE6B in the affected twins and their unaffected mother. Both variants segregated with disease in the family. Analysis of the relative expression of PDE6B , in peripheral blood cells, also revealed a significantly lower level of PDE6B transcript in affected siblings compared to a normal control. PDE6B is associated with recessive rod-cone degeneration and autosomal dominant congenital stationary night blindness. Ophthalmic evaluation of these patients showed night blindness, fundus abnormalities, and peripheral vision loss, which are consistent with PDE6B -associated recessive retinal degeneration. These findings suggest that the loss of PDE6B transcript resulting from the compound heterozygous pathogenic variants is the underlying cause of recessive rod-cone degeneration in the study family.
(© 2022 Sangermano et al.; Published by Cold Spring Harbor Laboratory Press.)
(© 2022 Sangermano et al.; Published by Cold Spring Harbor Laboratory Press.)