Whole genome sequencing in a Knobloch syndrome family confirms the molecular diagnosis

CONCLUSION: To date, all confirmed genetic diagnoses of Knobloch syndrome are attributable to variants in COL18A1. The family described here has a heterozygous novel loss of function variant. Detailed analysis of WGS data combined with family segregation studies concluded that although Asp1672Asn has a high population frequency, it is the most likely second pathogenic variant in our family. This supports the hypothesis that this is a hypomorphic allele, which, in combination with a loss of function pathogenic variant, leads to Knobloch syndrome.To our knowledge, this is the first time that WGS has been used to confirm a molecular diagnosis of Knobloch syndrome in this way and has provided further insight into the molecular mechanisms in this rare disorder.PMID:34751625 | DOI:10.1080/13816810.2021.1998554

Source: Ophthalmic Genetics - November 9, 2021 Category: Opthalmology Authors: Chetan Khantibai Patel Suzanne Broadgate Ahmed Shalaby Jing Yu Andrea H Nemeth Susan M Downes Stephanie Halford Source Type: research