Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site of causing North Carolina macular dystrophy in Korea.

PURPOSE

Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families.

METHODS

The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools.

RESULTS

We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of .

CONCLUSION

We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of .