GPSM2 and Chudley-McCullough syndrome: a Dutch founder variant brought to North America

Am J Med Genet A. 2013 May;161A(5):973-6. doi: 10.1002/ajmg.a.35808. Epub 2013 Mar 13.

Abstract

Chudley-McCullough syndrome (CMS) is characterized by profound sensorineural hearing loss and brain anomalies. Variants in GPSM2 have recently been reported as a cause of CMS by Doherty et al. In this study we have performed exome sequencing of three CMS patients from two unrelated families from the same Dutch village. We identified one homozygous frameshift GPSM2 variants c.1473delG in all patients. We show that this variant arises from a shared, rare haplotype. Since the c.1473delG variant was found in Mennonite settlers, it likely originated in Europe. To support DNA diagnostics, we established an LOVD database for GPSM2 containing all variants thus far described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Agenesis of Corpus Callosum / genetics*
  • Arachnoid Cysts / genetics*
  • Child, Preschool
  • Europe
  • Exome / genetics*
  • Female
  • Founder Effect
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mutation
  • Netherlands
  • North America
  • Pedigree
  • Sequence Analysis, DNA

Substances

  • GPSM2 protein, human
  • Intracellular Signaling Peptides and Proteins

Supplementary concepts

  • Chudley-Mccullough syndrome