ArticleAmerican journal of human genetics1996
Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A.
Article in American journal of human genetics, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Trial
- Whole-Exome Sequencing Identified a Nonsense Pathogenic Variant in the MITF Gene Associated with Non-syndromic Hearing Loss.Biochemical genetics · 2026Article
- Differential Expression ofAnimals : an open access journal from MDPI · 2026Article
- Article
- New Insights into Melanoma Tumor Syndromes.JID innovations : skin science from molecules to population health · 2022Review
- Analysis of genotype-phenotype relationships in 90 Chinese probands with Waardenburg syndrome.Human genetics · 2022Article
- Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation.BMC medical genomics · 2021Article
- Identification of novel MITF mutations in Chinese families with Waardenburg syndrome type II.Molecular genetics & genomic medicine · 2021Article
- CRISPR/Cas9-mediated correction ofMolecular therapy. Nucleic acids · 2021Article
- Four mutations in MITF, SOX10 and PAX3 genes were identified as genetic causes of waardenburg syndrome in four unrelated Iranian patients: case report.BMC pediatrics · 2021Article
- Frameshift variant in MITF gene in a large family with Waardenburg syndrome type II and a co-segregation of a C2orf74 variant.PloS one · 2021Article
- Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing theJournal of pediatric genetics · 2020Article
- A rare case of Waardenburg syndrome with unilateral hearing loss caused by nonsense variant c.772C>T (p.Arg259*) in theInternational journal of circumpolar health · 2019Article
- Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period.Iranian journal of public health · 2019Article
- Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations.Journal of human genetics · 2018Article
- Interstitial Chromosome 3p13p14 Deletions: An Update and Review.Molecular syndromology · 2018Review
- A Comprehensive Genetic and Clinical Evaluation of Waardenburg Syndrome Type II in a Set of Iranian Patients.International journal of molecular and cellular medicine · 2018Article
- Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss.PloS one · 2018Article
- Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis.Human genetics · 2017Article
- Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2.Journal of human genetics · 2017Article
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5 authors.
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Abstract
Waardenburg syndrome type 2 (WS2) is a dominantly inherited disorder characterized by a pigmentation anomaly and hearing impairment due to lack of melanocyte. Previous work has linked a subset of families with WS2 (WS2A) to the MITF gene that encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif and that is involved in melanocyte differentiation. Several splice-site and missense mutations have been reported in individuals affected with WS2A. In this report, we have identified two novel point mutations in the MITF gene in affected individuals from two different families with WS2A. The two mutations (C760--> T and C895--> T) create stop codons in exons 7 and 8, respectively. Corresponding mutant alleles predict the truncated proteins lacking HLH-Zip or Zip structure. To understand how these mutations cause WS2 in heterozygotes, we generated mutant MITF cDNAs and used them for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose the DNA-binding activity and fail to transactivate the promoter of tyrosinase, a melanocyte-specific enzyme. However, these mutated proteins do not appear to interfere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the phenotypes of the two families with WS2A in the present study are caused by loss-of-function mutations in one of the two alleles of the MITF gene, resulting in haploinsufficiency of the MITF protein, the protein necessary for normal development of melanocytes.
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