CPAMD8 loss-of-function in a family with non-dominant congenital glaucoma and anterior segment dysgenesis.

Abstract

Purpose : The main objective of this study was to identify diseases-causing variants in a patient diagnosed with non-dominant congenital glaucoma and ASD.

Methods : Trio whole exome sequencing was performed by next generation sequencing (NGS) with Illumina Hi Seq technology. Filtering with available genomic databases and in silico analyses were used to identify pathogenic variants. All pathogenic variants found were confirmed by Sanger sequencing. CPAMD8 transcript expression was analyzed by quantitative real time PCR. The analysis of the patient's trabeculectomy were performed by light microscopy and electron transmission microscopy.

Results : Trio whole-exome sequencing identified two compound heterozygous variants (p.(Lys845fsTer13) and p.(Arg668Ter)) in CPAMD8, a gene of unknown function and recently associated with ASD. Bioinformatic and quantitative real-time PCR analysis supported a loss-of-function pathogenic mechanism. Histologic examination of the trabeculectomy specimen from this patient revealed an immature anterior chamber angle, with anterior insertion of the ciliary muscle, altered extracellular matrix and apoptosis in the trabecular meshwork.

Conclusions : Our data support that CPAMD8 disruption underlies recessive CG and ASD associated with extracellular matrix disruption and provide new insights on the pathogenesis of this disease.

This is a 2020 ARVO Annual Meeting abstract.