TY - JOUR
T1 - Novel and recurrent non-truncating mutations of the MITF basic domain
T2 - Genotypic and phenotypic variations in Waardenburg and Tietz syndromes
AU - Léger, Sandy
AU - Balguerie, Xavier
AU - Goldenberg, Alice
AU - Drouin-Garraud, Valérie
AU - Cabot, Annick
AU - Amstutz-Montadert, Isabelle
AU - Young, Paul
AU - Joly, Pascal
AU - Bodereau, Virginie
AU - Holder-Espinasse, Muriel
AU - Jamieson, Robyn V.
AU - Krause, Amanda
AU - Chen, Hongsheng
AU - Baumann, Clarisse
AU - Nunes, Luis
AU - Dollfus, Hélène
AU - Goossens, Michel
AU - Pingault, Véronique
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
KW - freckles
KW - MITF
KW - pigmentation
KW - Tietz syndrome
KW - Waardenburg syndrome
UR - http://www.scopus.com/inward/record.url?scp=84862823103&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2011.234
DO - 10.1038/ejhg.2011.234
M3 - Article
C2 - 22258527
AN - SCOPUS:84862823103
SN - 1018-4813
VL - 20
SP - 584
EP - 587
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 5
ER -