Novel and recurrent non-truncating mutations of the MITF basic domain: Genotypic and phenotypic variations in Waardenburg and Tietz syndromes

Sandy Léger, Xavier Balguerie, Alice Goldenberg, Valérie Drouin-Garraud, Annick Cabot, Isabelle Amstutz-Montadert, Paul Young, Pascal Joly, Virginie Bodereau, Muriel Holder-Espinasse, Robyn V. Jamieson, Amanda Krause, Hongsheng Chen, Clarisse Baumann, Luis Nunes, Hélène Dollfus, Michel Goossens, Véronique Pingault

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper transcription factor, which regulates melanocyte development and the biosynthetic melanin pathway. A notable relationship has been described between non-truncating mutations of its basic domain and Tietz syndrome, which is characterized by albinoid-like hypopigmentation of the skin and hair, rather than the patchy depigmentation seen in Waardenburg syndrome, and severe hearing loss. Twelve patients with new or recurrent non-truncating mutations of the MITF basic domain from six families were enrolled in this study. We observed a wide range of phenotypes and some unexpected features. All the patients had blue irides and pigmentation abnormalities that ranged from diffuse hypopigmentation to Waardenburg-like patches. In addition, they showed congenital complete hearing loss, diffuse hypopigmentation of the skin, freckling and ocular abnormalities, more frequently than patients with MITF mutations outside the basic domain. In conclusion, the non-truncating mutations of the basic domain do not always lead to Tietz syndrome but rather to a large range of phenotypes. Sun-exposed freckles are interestingly observed more frequently in Asian populations. This variability argues for the possible interaction with modifier loci.

Original languageEnglish
Pages (from-to)584-587
Number of pages4
JournalEuropean Journal Of Human Genetics
Volume20
Issue number5
DOIs
Publication statusPublished - 1 May 2012

Keywords

  • freckles
  • MITF
  • pigmentation
  • Tietz syndrome
  • Waardenburg syndrome

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