June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
North Carolina Macular Dystrophy (NCMD/MCDR1): Haplotype analysis shows single ancestral founder in 13 American families
Author Affiliations & Notes
  • Kent W Small
    Retina, Molecular Insight Research Foundation, Los Angeles, California, United States
    Macula and Retina Institute, Glendale, California, United States
  • Edwin M Stone
    Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
  • Monique J Leys
    Ophthalmology, WVU Eye Institute, Morgantown, West Virginia, United States
  • Richard Alan Lewis
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Steven Agemy
    SUNY Downstate Medical Center, Brooklyn, California, United States
  • Charles A Garcia
    Ophthalmology-Herman Eye Ctr, University of Texas Houston Medical School, Houston, Texas, United States
  • Todd Schneiderman
    Ophthalmology, Retina Center Northwest, Silverdale, Washington, United States
  • Thomas A Rice
    VA Palo Alto Health Care System, Palo Alto, California, United States
  • Fadi Shaya
    Retina, Molecular Insight Research Foundation, Los Angeles, California, United States
    Macula and Retina Institute, Glendale, California, United States
  • Footnotes
    Commercial Relationships   Kent Small, None; Edwin Stone, None; Monique Leys, None; Richard Lewis, None; Steven Agemy, None; Charles Garcia, None; Todd Schneiderman, None; Thomas Rice, None; Fadi Shaya, None
  • Footnotes
    Support  Foundation Fighting Blindness Grant #: BR-GE-1216-0715-CSH
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4462. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Kent W Small, Edwin M Stone, Monique J Leys, Richard Alan Lewis, Steven Agemy, Charles A Garcia, Todd Schneiderman, Thomas A Rice, Fadi Shaya; North Carolina Macular Dystrophy (NCMD/MCDR1): Haplotype analysis shows single ancestral founder in 13 American families. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4462.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : North Carolina Macular Dystrophy (NCMD / MCDR1) is an autosomal dominant congenital developmental disorder of the macula with highly variable expressivity. Small et al mapped NCMD by linkage in 1991 to chromosome 6q16 in the original single large family from North Carolina and found the first 5 mutations in 2016. The first mutation found was a single base pair change (Chr 6: 99593030 G>T, Hg38) in a non-coding region of a DNASE1 site (designated “V1”) presumably affecting the expression of PRDM13. Subsequently, Small et al. have found over 40 families with the NCMD phenotype, 13 of which have the V1 mutation. Because all of these 13 are American, we suspected that there may be a single common founder despite no known genealogical connections among them.

Methods : We performed haplotype analyses of these 13 American NCMD families. If these 13 families have a common founder for NCMD then a shared region of DNA on chromosome 6q16 should be evident. Genotyping of the 13 NCMD families with V1 mutations was performed using 11 polymorphic short tandem repeats (STRs) within the 4,528,000 bp region centered on the MCDR1 / PRDM13 region. Four of the STR polymorphic markers were newly developed by our lab specifically to study this genomic region in these families. The computer program, Progeny, was utilized to construct the haplotypes from the raw genotype data.

Results : All 13 families showed overwhelming evidence of a common shared genomic haplotype for all 11 STR markers for the MCDR1 region on chromosome 6q16.This is apparently a unique haplotype for American NCMD patients as no such evidence was found in the other NCMD families with the other NCMD mutation. Twelve of the 13 families are Caucasian and one is African American.

Conclusions : The shared haplotype in these 13 families indicates that there is a single common founder for NCMD in the United States. None of these 13 American families have any known genealogical relationship with each other. The V1 mutation and this haplotype have only been found in Americans while the V2 mutation has been found in Europeans and some Americans. Currently there are a total of 9 distinct mutations causing NCMD and each one seems to be a new unique mutation. Three are point mutations in non-coding regions in the MCDR1 locus and remainder are duplications in the MCDR1 and MCDR3 loci.

This is a 2020 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×