biostudies-literatureChassaing NRetina FranceClinical Research Hospital Program from the French Ministry of Health474-85https://www.ebi.ac.uk/biostudies/studies/S-EPMC4817771biostudies-literatureUnknown26(4)Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers. To identify novel ODA loci, we conducted targeted high-throughput sequencing of 407 candidate genes in an initial cohort of 22 sporadic ODA patients. Patched 1 (PTCH1), an inhibitor of sonic hedgehog (SHH) signaling, harbored an enrichment of rare heterozygous variants in comparison to either controls, or to the other candidate genes (four missense and one frameshift); targeted resequencing of PTCH1 in a second cohort of 48 ODA patients identified two additional rare nonsynonymous changes. Using muGenome researchTargeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.PMC4817771PHRC 09 109 01McKnight KLDufier JLLamarre SCalvas PRossi MLacombe DDollfus HCausse ANiederriter ARCoubes CVincent-Delorme CKatsanis NDavid VChassaing NDavis EEDesmaison APasquier LKaplan JEtchevers HCFaguer SfalseTargeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers. To identify novel ODA loci, we conducted targeted high-throughput sequencing of 407 candidate genes in an initial cohort of 22 sporadic ODA patients. Patched 1 (PTCH1), an inhibitor of sonic hedgehog (SHH) signaling, harbored an enrichment of rare heterozygous variants in comparison to either controls, or to the other candidate genes (four missense and one frameshift); targeted resequencing of PTCH1 in a second cohort of 48 ODA patients identified two additional rare nonsynonymous changes. Using mu2016-01-01T00:00:00Z2016 Apr2026-05-04T08:07:29.69Z2019-03-27T03:10:58ZS-EPMC48177712689345910.1101/gr.196048.115