New Term Request: Macular retinal dystrophy 1, North Carolina type

[vjenkinsFB]

I'd like to request a term for macular retinal dystrophy 1, North Carolina type. This disorder is a little unusual genomically - it is a mutation in a DNaseI hypersensitivity site that affects two genes, PRDM13 (considered responsible for this disorder) and CCNC. I'm also not married to that name, and not sure which parent is best - I'll leave all that up to you.

OMIM: https://omim.org/entry/136550

Potential definition: Macular retinal dystrophy 1, North Carolina type has_material_basis_in heterozygous mutation in a DNase I hypersensitivity site on chromosome 6q16, upstream of the PRDM13 gene.

Potential parent term: macular degeneration OR retinal degeneration

Synonyms: macular dystrophy 1, North Carolina type; North Carolina macular dystrophy; MCDR1

ClinVar search term: had to do this backwards to figure out how they represented the DNaseI HS site: https://www.ncbi.nlm.nih.gov/clinvar/?term=%22North+Carolina+macular+dystrophy%22

MedGen page(s) pointed to by the above: https://www.ncbi.nlm.nih.gov/medgen/C0730294/ North Carolina macular dystrophy

MalaCards page: https://www.malacards.org/card/macular_dystrophy_retinal_1_north_carolina_type

HGNC entry for gene: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/13998

Citations other than those in the OMIM entry: there are tons of papers on this

• https://pubmed.ncbi.nlm.nih.gov/30578494/ Tsang SH, Sharma T. North Carolina Macular Dystrophy. Adv Exp Med Biol. 2018;1085:109-110. doi:10.1007/978-3-319-95046-4_21
• https://pubmed.ncbi.nlm.nih.gov/36243009/ Van de Sompele S, Small KW, Cicekdal MB, et al. Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy. Am J Hum Genet. 2022;109(11):2029-2048. doi:10.1016/j.ajhg.2022.09.013
• https://pubmed.ncbi.nlm.nih.gov/34125159/ Green DJ, Lenassi E, Manning CS, et al. North Carolina Macular Dystrophy: Phenotypic Variability and Computational Analysis of Disease-Associated Noncoding Variants. Invest Ophthalmol Vis Sci. 2021;62(7):16. doi:10.1167/iovs.62.7.16

Other links: https://eyewiki.aao.org/North_Carolina_Macular_Dystrophy

FlyBase paper(s) to curate with this term: FBrf0237158

My contact info: vjenkins@morgan.harvard.edu (FlyBase), 0000-0002-1567-7626. Thank you!

[lschriml]

Thank you for the new term !! Agreed, we will add this term and the others in this phenotypic series, as child terms of : macular degeneration (DOID:4448)

4 terms to add: https://www.omim.org/phenotypicSeries/PS136550 can also add in a parent term: OMIM:PS136550 retinal macular dystrophy retinal macular dystrophy 1, North Carolina type (OMIM:136550) GARD:9179, ORDO:75327 retinal macular dystrophy 2 (OMIM:608051) retinal macular dystrophy 3 (OMIM:/608850) retinal macular dystrophy 4 (OMIM:619977)

Cheers, Lynn

[allenbaron]

The existing 'cone-rod dystrophy 7' (DOID:0111012) in DO was suggested to be the same as one of the new diseases in this phenotypic series, 'retinal macular dystrophy 2' in:

Martin-Gutierrez MP, Schiff ER, Wright G, Waseem N, Mahroo OA, Michaelides M, Moore AT, Webster AR, Arno G; Genomics England Research Consortium. Dominant Cone Rod Dystrophy, Previously Assigned to a Missense Variant in RIMS1, Is Fully Explained by Co-Inheritance of a Dominant Allele of PROM1. Invest Ophthalmol Vis Sci. 2022 Aug 2;63(9):14. doi: 10.1167/iovs.63.9.14. PMID: 35947379; PMCID: PMC9381847.

This information has been provided to OMIM. The addition of 'retinal macular dystrophy 2' will await their determination.

[allenbaron]

The requested disease is named 'North Carolina macular dystrophy' and will be in the next release as DOID:0070439.

[allenbaron]

OMIM has updated the RIMS1 mutation identified in connection with CORD7 as a 'variant of unknown significance' and added information on these patients to CORD12, which is caused by PROM1. There's still a prominent genetic linkage to the CORD phenotype on chromosome 6q13 so CORD7 will likely not be deprecated. The definition for CORD7 has been updated accordingly with the publication of Martin-Gutierrez, et al. added as source to both CORD7 and CORD12.

At this time, no updates have been made to 'retinal macular dystrophy 2' (MCDR2), which shares as it's genetic cause mutation of the PROM1 gene with CORD12, Retinitis pigmentosa 41, and Stargardt disease 4. Among those, the MCDR2, CORD12, and Stargardt disease 4 phenotypes have all been described as caused by the R373C variant (with additional differing variants causing each).

[lschriml]

@allenbaron -- Can you please check again with OMIM ?

[allenbaron]

OMIM has updated CORD7 and MCDR2 but has not merged them. I've created MCDR2 which will be in the next release.