Poster presentation, P47

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

A novel non-truncating mutation of the MITF basic domain in an atypical form of type II Waardenburg syndrome

SPEAKER S. Léger #whois submiter ?
AUTHOR(s) S. Léger, X. Balguerie, A. Goldenberg, V. Drouin-Garraud, A. Cabot, I. Amstutz-Montadert, P. Young, P. Joly, M. Goossens, V. Pingault

BACKGROUND: The microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix (bHLH) leucine zipper transcription factor which regulates melanocyte development and biosynthetic melanin pathway. The basic domain of bHLH factors is their DNA binding domain, necessary to recognize and bind their transcriptional targets. A noteworthy relationship has been described between non-truncating mutations of the MITF basic domain and Tietz syndrome, which is characterized by an severe hearing loss and an albinoid-like hypopigmentation of the skin and hair, rather than the patchy depigmentation seen in Waardenburg syndrome (WS). OBSERVATION: Six family members were affected on three generations with relative similar phenotype. They lived in France and had both Vietnamese and Martinique origins. The proband was a 9-year-old boy who consulted for marked premature greying affecting eyelashes and eyebrows. He also had blue irides and generalized hypopigmentation of the skin, in contrast with familial dark phototype, associated with patchy depigmentation macules, freckles in sun-exposed regions, lentigines, cafe-au-lait macules. His auditory function was normal. RESULTS: A nucleotide substitution in the MITF gene, c.635T>G, that predicts a missense variation at the protein level (p.Ile212Ser) was found in all the affected members of this family. According to 3D models of other bHLH factors, the mutated amino-acid is expected to be on the side of the basic domain α-helix that is localized in contact with the DNA groove. CONCLUSION: This family strongly differs from the other cases of mutations located in the basic domain by the lack of congenital hearing loss over several generations. This precludes its classification as Tietz syndrome despite the uniform dilution of skin pigmentation. We also observed a striking high number of freckles as well as lentigines and café-au-lait macules. These pigmentary features are not considered as part of WS and therefore might be underestimated.



Advertisement from our sponsor:
Astellas Pharma Worldwide

Université de Bordeaux 2 & Conseil Régional Aquitaine