title: Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes.
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.
authors.affiliation: Clinique Dermatologique, INSERM U905, Rouen University Hospital, Rouen, France.
authors.forename: Sandy
authors.initials: S
authors.lastname: Léger
authors.forename: Xavier
authors.initials: X
authors.lastname: Balguerie
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Annick
authors.initials: A
authors.lastname: Cabot
authors.forename: Isabelle
authors.initials: I
authors.lastname: Amstutz-Montadert
authors.forename: Paul
authors.initials: P
authors.lastname: Young
authors.forename: Pascal
authors.initials: P
authors.lastname: Joly
authors.forename: Virginie
authors.initials: V
authors.lastname: Bodereau
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Robyn V
authors.initials: RV
authors.lastname: Jamieson
authors.forename: Amanda
authors.initials: A
authors.lastname: Krause
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.forename: Luis
authors.initials: L
authors.lastname: Nunes
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Véronique
authors.initials: V
authors.lastname: Pingault
mesh_terms: D000328:Adult; D016115:Albinism, Oculocutaneous / Q000235:genetics*; D002675:Child, Preschool; D003638:Deafness / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: D051739:Microphthalmia-Associated Transcription Factor