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Three severe cases of EBS Dowling-Meara caused by missense and frameshift mutations in the keratin 14 gene

Matthias Titeux1, Juliette Mazereeuw-Hautier, Smaïl Hadj-Rabia

  • 1INSERM, U563, Toulouse, France.

The Journal of Investigative Dermatology
|January 28, 2006
PubMed

Insights

Severe epidermolysis bullosa simplex Dowling-Meara type (EBS-DM) in infants results from KRT14 mutations. A novel mutation showed improvement, unlike a previously described one, highlighting genotype-phenotype correlations for genetic counseling.

Area of Science:

  • Genetics
  • Dermatology
  • Molecular Biology

Background:

  • Epidermolysis Bullosa Simplex Dowling-Meara type (EBS-DM) is a severe inherited blistering skin disorder.
  • Mutations in the KRT14 gene, encoding keratin 14, are a known cause of EBS-DM.

Purpose of the Study:

  • To investigate genotype-phenotype correlations in three unrelated patients with severe EBS-DM.
  • To characterize a novel KRT14 mutation and compare its clinical impact to a known mutation.

Main Methods:

  • Clinical assessment of three patients presenting with severe EBS-DM at birth.
  • Genetic analysis, including sequencing of the KRT14 gene, to identify causative mutations.
  • Correlation of identified mutations with clinical phenotypes and disease severity over time.

Main Results:

  • Two patients were heterozygous for the previously identified p.M119T mutation in KRT14, exhibiting severe EBS-DM.
  • A third patient, heterozygous for a novel c.1246delC mutation in KRT14, showed clinical improvement by age two.
  • The novel mutation results in a 25 amino-acid aberrant carboxyterminal sequence, affecting keratin 14 structure.

Conclusions:

  • Genotype-phenotype correlations are evident in EBS-DM, with different KRT14 mutations leading to varying disease severity and progression.
  • The novel c.1246delC mutation represents a less severe variant compared to the p.M119T mutation.
  • These findings have significant implications for genetic counseling and understanding the molecular basis of EBS-DM.

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