Total absence of the alpha2(I) chain of collagen type I causes a rare form of Ehlers-Danlos syndrome with hypermobility and propensity to cardiac valvular problems

J Med Genet. 2006 Jul;43(7):e36. doi: 10.1136/jmg.2005.038224.

Abstract

Background: Heterozygous mutations in the COL1A1 or COL1A2 gene encoding the alpha1 and alpha2 chain of type I collagen generally cause either osteogenesis imperfecta or the arthrochalasis form of Ehlers-Danlos syndrome (EDS). Homozygous or compound heterozygous COL1A2 mutations resulting in complete deficiency of the proalpha2(I) collagen chains are extremely rare and have been reported in only a few patients, albeit with variable phenotypic outcome.

Methods: The clinical features of the proband, a 6 year old boy, were recorded. Analysis of proalpha and alpha-collagen chains was performed by SDS-polyacrylamide gel electrophoresis using the Laemmli buffer system. Single stranded conformation polymorphism analysis of the proband's DNA was also carried out.

Results: In this report we show that complete lack of proalpha2(I) collagen chains can present as a phenotype reminiscent of mild hypermobility EDS during childhood.

Conclusions: Biochemical analysis of collagens extracted from skin fibroblasts is a powerful tool to detect the subset of patients with complete absence of proalpha2(I) collagen chains, and in these patients, careful cardiac follow up with ultrasonography is highly recommended because of the risk for cardiac valvular problems in adulthood.

Publication types

  • Case Reports
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Collagen / genetics*
  • Collagen Type I
  • Consanguinity
  • Ehlers-Danlos Syndrome / genetics*
  • Female
  • Foot Deformities
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Hand Deformities
  • Heart Valve Diseases / genetics*
  • Humans
  • Male
  • Motor Activity
  • Polymorphism, Single-Stranded Conformational

Substances

  • Collagen Type I
  • Collagen