Genetic insights into Tietz albinism-deafness syndrome: A new dominant-negative mutation in MITF.

Autor: Yamamoto K; Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan., Okamura K; Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan., Wakamatsu K; Institute for Melanin Chemistry, Fujita Health University, Toyoake, Japan., Ito S; Institute for Melanin Chemistry, Fujita Health University, Toyoake, Japan., Akabane K; Department of Ophthalmology, Faculty of Medicine, Yamagata University, Yamagata, Japan., Arai Y; Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan., Kawaguchi J; Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan., Hozumi Y; Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan., Suzuki T; Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Jazyk: angličtina
Zdroj: Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2024 Jul; Vol. 37 (4), pp. 430-437. Date of Electronic Publication: 2024 Mar 04.
DOI: 10.1111/pcmr.13166
Abstrakt: Tietz albinism-deafness syndrome (TADS) is a rare and severe manifestation of Waardenburg syndrome that is primarily linked to mutations in MITF. In this report, we present a case of TADS resulting from a novel c.637G>C mutation in MITF (p.Glu213Gln; GenBank Accession number: NM_000248). A 3-year-old girl presented with congenital generalized hypopigmentation of the hair, skin, and irides along with complete sensorineural hearing loss. Histopathological and electron microscopy investigations indicated that this variant did not alter the number of melanocytes in the skin but significantly impaired melanosome maturation within melanocytes. Comprehensive melanin analysis revealed marked reductions in both eumelanin (EM) and pheomelanin (PM) rather than changes in the EM-to-PM ratio observed in oculocutaneous albinism. We conducted an electrophoretic mobility shift assay to investigate the binding capability of the identified variant to DNA sequences containing the E-box motif along with other known variants (p.Arg217del and p.Glu213Asp). Remarkably, all three variants exhibited dominant-negative effects, thus providing novel insights into the pathogenesis of TADS. This study sheds light on the genetic mechanisms underlying TADS and offers a deeper understanding of this rare condition and its associated mutations in MITF.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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