Human Disease Model Report: macular retinal dystrophy 1, North Carolina type

General Information

Name

macular retinal dystrophy 1, North Carolina type

FlyBase ID

FBhh0000798

Disease Ontology Term

North Carolina macular dystrophy

Parent Disease

OMIM

MACULAR DYSTROPHY, RETINAL, 1, NORTH CAROLINA TYPE; MCDR1

Overview

Macular retinal dystrophy 1, North Carolina type (MCDR1 or NCMD), a form of autosomal dominant inherited macular dystrophy. MCDR1 is associated with heterozygous mutation in a DNase I hypersensitivity site on chromosome 6 (DHS6S1), upstream of both the PRDM13 gene (which encodes a transcription factor) and the divergently transcribed CCNC gene (which encodes a ubiquitous cell cycle controller). Discovery of duplications in this region in some families with MCDR1 has led to the hypothesis that overexpression of one of these two genes is the causative factor; PRDM13 is the stronger candidate. Experiments in flies, using the Drosophila genes orthologous to PRDM13 and CCNC, Dmel\Prdm13 and Dmel\CycC, support the role of PRDM13 in development of this disease.

The human PRDM13 gene has not been introduced into flies.

Knock-down or overexpression of Dmel\Prdm13 or Dmel\CycC were induced in the developing eye. Knockdown of either gene, effected by RNAi, had no effect. Overexpression of CycC also had no effect. Overexpression of Prdm13 led to a severe loss of cells of the imaginal eye-antennal disc. Physical interactions of Dmel\Prdm13 have been described; see below and in the Prdm13 gene report.

[updated June 2025 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: macular retinal dystrophy 1, North Carolina type

OMIM report

[MACULAR DYSTROPHY, RETINAL, 1, NORTH CAROLINA TYPE; MCDR1](https://omim.org/entry/136550)

Human gene(s) implicated

[DNase1 HYPERSENSITIVITY, CHROMOSOME 6, SITE 1; DHS6S1](https://omim.org/entry/616842)

Symptoms and phenotype

Macular dystrophy causes deterioration of the most sensitive part of the central retina (macula), which has the highest concentration of photoreceptors; the photoreceptors in this region are responsible for central vision and color perception. (http://www.allaboutvision.com/conditions/macular-dystrophy.htm)

(FlyBase Curators, 2013-)

North Carolina macular dystrophy is generally nonprogressive. The ophthalmoscopic findings are highly variable and are more dramatic than one would predict from the relatively good visual acuity level. Patients may have only a few drusen in the central macular region (grade I), confluent drusen confined to the central macular region (grade II), or a severe macular coloboma/staphyloma (grade III) involving 3 to 4 disc areas of the central macular region. Color vision is normal. Electrophysiologic studies are also normal (summary by Small, 1998). [from MIM:136550; 2018.05.02]

(OMIM, 2013-)

Genetics

PRDM13 has been associated with age-related macular degeneration in a GWAS study (see GWAS Catalog, below in 'External links').

(FlyBase Curators, 2013-)

North Carolina macular dystrophy (NCMD, MCDR1) is a congenital autosomal dominant trait that appears to be completely penetrant. MCDR1 is associated with heterozygous mutation in a DNase I hypersensitivity site on chromosome 6q16 (DHS6S1), upstream of the PRDM13 gene [from MIM:136550; 2018.05.02]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

DHS6S1 is located approximately 13 kb upstream of the PRDM13 gene, which encodes a retinal transcription factor, and approximately 23 kb upstream of the CCNC gene, which lies in the opposite orientation to PRDM1 and encodes a ubiquitous cell cycle controller. [from MIM:616842; 2018.05.02]

(OMIM, 2013-)

PRDM13 belongs to the PRDM family of transcription factors, which contain a PR domain and a variable number of zinc finger domains (Chang et al., 2013; pubmed:23639443). [from MIM:616741; 2018.05.02]

(OMIM, 2013-)

External links