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Microphthalmia\u2010associated transcription factor (<jats:italic>MITF<\/jats:italic>) is one of its significant pathogenic genes. Despite the comprehensive investigation in animal models, the pathogenic mechanism is still poorly described in humans due to difficulties accessing embryonic tissues. In this work, we used induced pluripotent stem cells derived from a WS patient carrying a heterozygous mutation in the <jats:italic>MITF<\/jats:italic> gene c.626A&gt;T (p.His209Leu), and differentiated toward melanocyte lineage, which is the most affected cell type involved in WS. Compared with the wild\u2010type cell line, the <jats:italic>MITF<\/jats:italic><jats:sup>mut<\/jats:sup> cell line showed a reduced expression of the characteristic melanocyte\u2010related genes and a lesser proportion of mature, fully pigmented melanosomes. The transcriptome analysis also revealed widespread gene expression changes at the melanocyte stage in the <jats:italic>MITF<\/jats:italic><jats:sup>mut<\/jats:sup> cell line. The differentially expressed genes were enriched in melanogenesis and cell proliferation\u2010related pathways. Interestingly, ion transport\u2010related genes also showed a significant difference in <jats:italic>MITF<\/jats:italic><jats:sup>mut<\/jats:sup>\u2010induced melanocytes, indicating that the <jats:italic>MITF<\/jats:italic> mutant may lead to the dysfunction of potassium channels and transporters produced by intermediate cells in the cochlea, further causing the associated phenotype of deafness. Altogether, our study provides valuable insights into how <jats:italic>MITF<\/jats:italic> mutation affects WS patients, which might result in defective melanocyte development and the related phenotype based on the patient\u2010derived iPSC model.<\/jats:p>","DOI":"10.1111\/pcmr.13118","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T05:26:27Z","timestamp":1691645187000},"page":"21-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modeling of pigmentation disorders associated with <i>MITF<\/i> mutation in Waardenburg syndrome revealed an impaired melanogenesis pathway in <scp>iPS<\/scp>\u2010derived melanocytes"],"prefix":"10.1111","volume":"37","author":[{"given":"Jie","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China  Changsha 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