First evidence of SOX2 mutations in Peters' anomaly: Lessons from molecular screening of 95 patients.

Anterior Eye Segment / abnormalities Comparative Genomic Hybridization Corneal Opacity / diagnosis DNA Copy Number Variations / genetics Eye Abnormalities / diagnosis Humans Mutation / genetics SOXB1 Transcription Factors / genetics

B3GLCT CNV CYP1B1 FOXE3 PAX6 PITX3 Peters' anomaly SOX2 anterior segment dysgenesis microphthalmia

Journal

Clinical genetics

ISSN: 1399-0004

Titre abrégé: Clin Genet

Pays: Denmark

ID NLM: 0253664

Informations de publication

Date de publication:
05 2022

Historique:

revised: 10 02 2022

received: 21 10 2021

accepted: 12 02 2022

pubmed: 17 2 2022

medline: 7 5 2022

entrez: 16 2 2022

Statut: ppublish

Résumé

Peters' anomaly (PA) is a rare anterior segment dysgenesis characterized by central corneal opacity and irido-lenticulo-corneal adhesions. Several genes are involved in syndromic or isolated PA (B3GLCT, PAX6, PITX3, FOXE3, CYP1B1). Some copy number variations (CNVs) have also been occasionally reported. Despite this genetic heterogeneity, most of patients remain without genetic diagnosis. We retrieved a cohort of 95 individuals with PA and performed genotyping using a combination of comparative genomic hybridization, whole genome, exome and targeted sequencing of 119 genes associated with ocular development anomalies. Causative genetic defects involving 12 genes and CNVs were identified for 1/3 of patients. Unsurprisingly, B3GLCT and PAX6 were the most frequently implicated genes, respectively in syndromic and isolated PA. Unexpectedly, the third gene involved in our cohort was SOX2, the major gene of micro-anophthalmia. Four unrelated patients with PA (isolated or with microphthalmia) were carrying pathogenic variants in this gene that was never associated with PA before. Here we described the largest cohort of PA patients ever reported. The genetic bases of PA are still to be explored as genetic diagnosis was unavailable for 2/3 of patients. Nevertheless, we showed here for the first time the involvement of SOX2 in PA, offering new evidence for its role in corneal transparency and anterior segment development.

Identifiants

DOI: 10.1111/cge.14123 PMID: 35170016

pubmed: 35170016

doi: 10.1111/cge.14123

doi:

Substances chimiques

SOX2 protein, human 0

SOXB1 Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

494-506

Informations de copyright

Références

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