CCM2 Exon 2-10 Deletion

The CCM2 Exon 2-10 Deletion (CCM2 Common Deletion) is a founder mutation in the United States. A founder mutation means that families with this specific defect of the CCM2 gene share a common ancestor and are distantly related. So far, we have connected families whose ancestors lived in South Carolina, Alabama, Mississippi, Louisiana, and Missouri.

Alliance to Cure Cavernous Malformation is working to find those who are affected in the hope of connecting these families and identifying the original founding couple. As of January 2022, we have connected more than 35 families in a Facebook group and have traced the mutation to the following ancestors who should connect at a point even further back in time.

  • Matthew Malachi Rushing and Sarah (Howell) Harrell, born in North or South Carolina in the 1760’s. Many of their descendants relocated to Amite/Franklin, Mississippi and are now scattered between Mississippi and Louisiana. This is the family with the largest number of people identified with the CCM2 exon 2-10 deletion.
  • Daniel Ward and his wife Rachel (last name unknown), born in South Carolina in the 1790’s. Their family relocated to Abbeville, Henry County, Alabama. Current descendants we know are in Alabama and in northern California.
  • James Oglesbee (born 1789 in Screven Georgia) and his wife Martha (possibly Martha Elizabeth Martin, born in South Carolina). This family lived in Mississippi and east Texas. Current descendants are in Texas and Mississippi.
  • William Bailey and Julia Ann Denny, who lived in Missouri in the early 1800s (William was born in Tennessee, we believe). Current descendants that we know are in California/Oregon and in Kansas.
  • Possibly Henry Farmer and Sarah Ward (born 1680-90 in Henrico, Virginia). Many of our families have roots in Varina, Henrico, Virginia and some connect here, but we don’t yet have enough evidence to say that this is a conclusive connection.

The story of the CCM2 exon 2-10 deletion and our work to find common ancestors was shared in The Atlantic in January 2022: https://www.theatlantic.com/science/archive/2022/01/brain-bleed-genetic-mutation-ccm2-deletion/621336/.

A joint research project with Duke University definitively concluded that the families who carry this specific mutation are related.  As of this writing, it is published as a pre-print.

Understanding the family tree is important for improving care for several reasons. It will help us:

  • find and connect more at-risk families;
  • identify geographic areas where we should put more resources into medical provider outreach to improve care; and
  • tie the illness to the story of states or regions, which can raise visibility among the public and among legislators who have an influence on research funding.

We would love to introduce patients affected by the CCM2 Exon 2-10 Deletion to our growing community of families via our closed Facebook group. We invite you to join this exciting project which now includes a professional genealogist. You don’t need to have extensive genealogical information to participate – that is what we do with the project.

To let us know you are interested, you can email Connie Lee at clee@alliancetocure.org. Make sure you include in your message that you are interested in the CCM2 Common Deletion Project.

References

Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, Marchuk DA. Deletions in CCM2 are a common cause of cerebral cavernous malformations. Am J Hum Genet. 2007 Jan;80(1):69-75.

Gallione CJ, Detter MR, Christmas HM, Lee C, Marchuk DA. Genetic Genealogy Uncovers a Founder Deletion Mutation in the Cerebral Cavernous Malformations 2 Gene. Human Genetics. Pre-print. DOI 10.21203/rs.3.rs-1167740/v1

Updated 1.24.22  Reviewed 4.17.22