{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["22(10)"],"submitter":["Ma A"],"pubmed_abstract":["<h4>Purpose</h4>Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, and genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, and pedigree structure data to achieve a genetic conclusion.<h4>Methods</h4>We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases.<h4>Results</h4>We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic cases were found to have heterozygous variants, which in most cases were de novo. Approximately one-third (7/22) of genetic diagnoses were found in rarely reported or recently identified ASD genes including PXDN, GJA8, COL4A1, ITPR1, CPAMD8, as well as the new phenotypic association of Axenfeld-Rieger anomaly with a homozygous ADAMTS17 variant. The remainder of the variants were in key ASD genes including FOXC1, PITX2, CYP1B1, FOXE3, and PAX6.<h4>Conclusions</h4>We demonstrate the benefit of detailed phenotypic, genomic, variant, and segregation analysis to uncover some of the previously \"hidden\" heritable answers in several rarely reported and newly identified ocular ASD-related disease genes."],"journal":["Genetics in medicine : official journal of the American College of Medical Genetics"],"pagination":["1623-1632"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7521990"],"repository":["biostudies-literature"],"pubmed_title":["Revealing hidden genetic diagnoses in the ocular anterior segment disorders."],"pmcid":["PMC7521990"],"pubmed_authors":["Holman KJ","Stutterd CA","Flaherty M","Grigg JR","Elder JE","Wilson M","Martin F","Amor DJ","Hackett EL","Yousoof S","Fisk K","Wong K","Farnsworth E","Enriquez A","Karaconji T","Nelson J","Jenkins G","Bennetts B","Cheng A","Cowley MJ","Jamieson RV","Ho G","Gayagay T","Dinger ME","Ma A","Kamien B","Nash BM","Minoche AE","Lai T"],"additional_accession":[]},"is_claimable":false,"name":"Revealing hidden genetic diagnoses in the ocular anterior segment disorders.","description":"<h4>Purpose</h4>Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, and genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, and pedigree structure data to achieve a genetic conclusion.<h4>Methods</h4>We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases.<h4>Results</h4>We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic cases were found to have heterozygous variants, which in most cases were de novo. Approximately one-third (7/22) of genetic diagnoses were found in rarely reported or recently identified ASD genes including PXDN, GJA8, COL4A1, ITPR1, CPAMD8, as well as the new phenotypic association of Axenfeld-Rieger anomaly with a homozygous ADAMTS17 variant. The remainder of the variants were in key ASD genes including FOXC1, PITX2, CYP1B1, FOXE3, and PAX6.<h4>Conclusions</h4>We demonstrate the benefit of detailed phenotypic, genomic, variant, and segregation analysis to uncover some of the previously \"hidden\" heritable answers in several rarely reported and newly identified ocular ASD-related disease genes.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2025-04-22T16:18:09.307Z","creation":"2025-02-19T01:10:20.734Z"},"accession":"S-EPMC7521990","cross_references":{"pubmed":["32499604"],"doi":["10.1038/s41436-020-0854-x"]}}