An autosomal recessive form of monilethrix is caused by mutations in DSG4: Clinical overlap with localized autosomal recessive hypotrichosis

Abraham Zlotogorski, Dina Marek, Liran Horev, Almogit Abu, Dan Ben-Amitai, Liora Gerad, Arieh Ingber, Moshe Frydman, Haike Reznik-Wolf, Daniel A. Vardy, Elon Pras

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Monilethrix is a structural defect of the hair shaft usually inherited in an autosomal dominant fashion and caused by mutations in the hHb1, hHb3, and hHb6 keratin genes. Autosomal recessive inheritance in this disease has been sporadically reported. We encountered 12 Jewish families from Iraq, Iran, and Morocco with microscopic findings of monilethrix, but with no evidence of vertical transmission. Since no mutations were found in these three hair keratin genes, we examined nine chromosomal regions containing gene clusters encoding skin and hair genes. On chromosome 18q, a common haplotype in the homozygous state was found among all seven Iraqi patients, but not in 20 controls (P≤0.0001). Sequencing of the main candidate gene from this region revealed four different mutations in desmoglein 4 (DSG4). Mutations in DSG4 have been previously reported in localized autosomal recessive hypotrichosis, a disorder that shares the clinical features of monilethrix but lacks the characteristic microscopic appearance of the hair shaft. Our findings have important implications for genetic counseling to monilethrix patients and families, and suggest that DSG4-associated hair disorders may be more common than previously thought.

Original languageEnglish
Pages (from-to)1292-1296
Number of pages5
JournalJournal of Investigative Dermatology
Volume126
Issue number6
DOIs
StatePublished - 1 Jun 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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