Lara K Holtes, Suzanne E de Bruijn, Frans P M Cremers, Susanne Roosing
{"title":"Dual inheritance patterns: a spectrum of non-syndromic inherited retinal disease phenotypes with varying molecular mechanisms.","authors":"Lara K Holtes, Suzanne E de Bruijn, Frans P M Cremers, Susanne Roosing","doi":"10.1016/j.preteyeres.2024.101308","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":null,"pages":null},"PeriodicalIF":18.6000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Retinal and Eye Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.preteyeres.2024.101308","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists.
The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.