TY - JOUR
T1 - Comparison of Worldwide Disease Prevalence and Genetic Prevalence of Inherited Retinal Diseases and Variant Interpretation Considerations
AU - Hanany, Mor
AU - Shalom, Sapir
AU - Ben-Yosef, Tamar
AU - Sharon, Dror
N1 - Publisher Copyright:
© 2024 Cold Spring Harbor Laboratory Press; all rights reserved;.
PY - 2024/2
Y1 - 2024/2
N2 - One of the considerations in planning the development of novel therapeutic modalities is disease prevalence that is usually defined by studying large national/regional populations. Such studies are rare and might suffer from inaccuracies and challenging clinical characterization in heterogeneous diseases, such as inherited retinal diseases (IRDs). Here we collect-ed reported disease prevalence information on various IRDs in different populations. The most common IRD, retinitis pigmentosa, has an average disease prevalence of ∼1:4500 individuals, Stargardt disease ∼1:17,000, Usher syndrome ∼1:25,000, Leber congenital am-aurosis ∼1:42,000, and all IRDs ∼1:3450. We compared these values to genetic prevalence (GP) calculated based on allele frequency of autosomal-recessive IRD mutations. Although most values did correlate, some differences were observed that can be explained by discor-dant, presumably null mutations that are likely to be either nonpathogenic or hypomorphic. Our analysis highlights the importance of performing additional disease prevalence studies and to couple them with population-dependent allele frequency data.
AB - One of the considerations in planning the development of novel therapeutic modalities is disease prevalence that is usually defined by studying large national/regional populations. Such studies are rare and might suffer from inaccuracies and challenging clinical characterization in heterogeneous diseases, such as inherited retinal diseases (IRDs). Here we collect-ed reported disease prevalence information on various IRDs in different populations. The most common IRD, retinitis pigmentosa, has an average disease prevalence of ∼1:4500 individuals, Stargardt disease ∼1:17,000, Usher syndrome ∼1:25,000, Leber congenital am-aurosis ∼1:42,000, and all IRDs ∼1:3450. We compared these values to genetic prevalence (GP) calculated based on allele frequency of autosomal-recessive IRD mutations. Although most values did correlate, some differences were observed that can be explained by discor-dant, presumably null mutations that are likely to be either nonpathogenic or hypomorphic. Our analysis highlights the importance of performing additional disease prevalence studies and to couple them with population-dependent allele frequency data.
UR - http://www.scopus.com/inward/record.url?scp=85184279286&partnerID=8YFLogxK
U2 - 10.1101/cshperspect.a041277
DO - 10.1101/cshperspect.a041277
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C2 - 37460155
AN - SCOPUS:85184279286
SN - 2157-1422
VL - 14
JO - Cold Spring Harbor Perspectives in Medicine
JF - Cold Spring Harbor Perspectives in Medicine
IS - 2
M1 - a041277
ER -