neurogenetics

, Volume 11, Issue 4, pp 465–470

GJB1/Connexin 32 whole gene deletions in patients with X-linked Charcot–Marie–Tooth disease

  • Claudia Gonzaga-Jauregui
  • Feng Zhang
  • Charles F. Towne
  • Sat Dev Batish
  • James R. Lupski
SHORT COMMUNICATION

DOI: 10.1007/s10048-010-0247-4

Cite this article as:
Gonzaga-Jauregui, C., Zhang, F., Towne, C.F. et al. Neurogenetics (2010) 11: 465. doi:10.1007/s10048-010-0247-4

Abstract

The X-linked form of Charcot–Marie–Tooth disease (CMTX) is the second most common form of this genetically heterogeneous inherited peripheral neuropathy. CMT1X is caused by mutations in the GJB1 gene. Most of the mutations causative for CMT1X are missense mutations. In addition, a few disease causative nonsense mutations and frameshift deletions that lead to truncated forms of the protein have also been reported to be associated with CMT1X. Previously, there have been reports of patients with deletions of the coding sequence of GJB1; however, the size and breakpoints of these deletions were not assessed. Here, we report five patients with deletions that range in size from 12.2 to 48.3 kb and that completely eliminate the entire coding sequence of the GJB1 gene, resulting in a null allele for this locus. Analyses of the breakpoints of these deletions showed that they are nonrecurrent and that they can be generated by different mechanisms. In addition to PMP22, GJB1 is the second CMT gene for which both point mutations and genomic rearrangements can cause a neuropathy phenotype, stressing the importance of CMT as a genomic disorder.

Keywords

Charcot–Marie–Tooth diseaseGJB1Connexin32Gene deletionGenomic rearrangement

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Claudia Gonzaga-Jauregui
    • 1
  • Feng Zhang
    • 1
    • 2
    • 3
  • Charles F. Towne
    • 4
  • Sat Dev Batish
    • 4
  • James R. Lupski
    • 1
    • 5
    • 6
  1. 1.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.State Key Laboratory of Genetic Engineering, School of Life SciencesFudan UniversityShanghaiChina
  3. 3.MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical SciencesFudan UniversityShanghaiChina
  4. 4.Athena Diagnostics, IncWorcesterUSA
  5. 5.Department of PediatricsBaylor College of MedicineHoustonUSA
  6. 6.Texas Children’s HospitalHoustonUSA