Dual inheritance patterns: a spectrum of non-syndromic inherited retinal disease phenotypes with varying molecular mechanisms.

Autor: Holtes LK; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands., de Bruijn SE; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands., Cremers FPM; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands., Roosing S; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: susanne.roosing@radboudumc.nl.
Jazyk: angličtina
Zdroj: Progress in retinal and eye research [Prog Retin Eye Res] 2024 Oct 30, pp. 101308. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1016/j.preteyeres.2024.101308
Abstrakt: Inherited retinal diseases (IRDs) encompass a variety of disease phenotypes and are known to display both clinical and genetic heterogeneity. A further complexity is that for several IRD-associated genes, pathogenic variants have been reported to cause either autosomal dominant (AD) or autosomal recessive (AR) diseases. The possibility of dual inheritance can create a challenge for variant interpretation as well as the genetic counselling of patients. This review aims to determine whether the molecular mechanisms behind the dual inheritance of each IRD-associated gene is well established, not yet properly understood, or if the association is questionable. Each gene is discussed individually in detail due to different protein structures and functions, but there are overlapping characteristics. For example, eight genes only have a limited number of reported pathogenic variants or a hotspot region implicated in the second inheritance pattern. Whereas CRX and RP1 display distinct spatial patterns for AR and AD pathogenic variants based on the variant type and/or location. The genes with a questionable dual inheritance, namely AIPL1, CRB1, and RCBTB1 highlight the importance of carefully considering allele frequency data. Finally, the crucial role relevant functional studies in animal and cell models play in validating a variant's biochemical or molecular effect is emphasised.
Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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