Case report: Disease phenotype associated with simultaneous biallelic mutations in ABCA4 and USH2A due to uniparental disomy of chromosome 1
Inherited retinal diseases (IRDs) represent a spectrum of clinically and genetically heterogeneous disorders. Our study describes an IRD patient carrying ABCA4 and USH2A pathogenic biallelic mutations as a result of paternal uniparental disomy (UPD) in chromosome 1. The proband is a 9-year-old girl...
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Published in | Frontiers in genetics Vol. 13 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
16.08.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Inherited retinal diseases (IRDs) represent a spectrum of clinically and genetically heterogeneous disorders. Our study describes an IRD patient carrying
ABCA4
and
USH2A
pathogenic biallelic mutations as a result of paternal uniparental disomy (UPD) in chromosome 1. The proband is a 9-year-old girl born from non-consanguineous parents. Both parents were asymptomatic and denied family history of ocular disease. Clinical history and ophthalmologic examination of the proband were consistent with Stargardt disease. Whispered voice testing disclosed moderate hearing loss. Next-generation sequencing and Sanger sequencing identified pathogenic variants in
ABCA4
(c.4926C>G and c.5044_5058del) and
USH2A
(c.2276G>T). All variants were present homozygously in DNA from the proband and heterozygously in DNA from the father. No variants were found in maternal DNA. Further analysis of single nucleotide polymorphisms confirmed paternal UPD of chromosome 1. This is the first known patient with confirmed UPD for two recessively mutated IRD genes. Our study expands on the genetic heterogeneity of IRDs and highlights the importance of UPD as a mechanism of autosomal recessive disease in non-consanguineous parents. Moreover, a long-term follow-up is essential for the identification of retinal features that may develop as a result of
USH2A
-related conditions. |
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Bibliography: | Edited by: Enrico Baruffini, University of Parma, Italy Hongbin L. V., Southwest Medical University, China This article was submitted to Genetics of Common and Rare Diseases, a section of the journal Frontiers in Genetics These authors share first authorship Reviewed by: Rando Allikmets, Columbia University, United States |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2022.949437 |