North Carolina macular dystrophy: mutations found in 12 additional families

Abstract

Purpose : Small and co-workers (Ophthalmology, 2016) recently showed that mutations affecting the expression of PRDM13 cause North Carolina macular dystrophy (NCMD / MCDR1). The purpose of this study was to investigate the PRDM locus in 12 additional families with this phenotype and to identify mutations causing North Carolina macular dystrophy (NCMD, MCDR1) in these families.

Methods : 18 new families with the NCMD phenotype (a total of 46 affected individuals) were studied using a combination of Sanger sequencing of the DNase I hypersensitivity site upstream of PRDM13 and PCR-based assay for the detection of a previously described duplication of the PRDM13 gene. IRB approval was obtained and informed consent was obtained from all participants.

Results : The original NCMD publication reported four different mutations (V1-V4) distributed among eleven different kindreds. To date, we have identified the disease-causing mutations in 12 new independent families with the NCMD phenotype. Seven of these harbor the previously described V1 mutation (all from the USA) and five families harbor the previously described V2 mutation (4 European, 1 USA). These two variants segregated perfectly in the 36 affected and 10 unaffected members of these 12 new NCMD families. No mutations have yet been identified in the other six families. We have an additional 6 families yet to be studied.

Conclusions : We identified 12 new families with disease-causing mutations in the DNase I hypersensitivity site upstream of the PRDM13 gene.
Additional families with the NCMD phenotype continue to support that these mutations are causative of MCDR1 / NCMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.