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Though heterozygous mutations in <jats:italic>MITF<\/jats:italic> are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in <jats:italic>MITF<\/jats:italic> in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in <jats:italic>MITF<\/jats:italic> and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.<\/jats:p>","DOI":"10.1002\/ajmg.a.60693","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T11:19:26Z","timestamp":1544786366000},"page":"243-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A homozygous <i>MITF<\/i> mutation leads to familial Waardenburg syndrome type 4"],"prefix":"10.1002","volume":"179","author":[{"given":"Xiuhong","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery Taizhou People's Hospital, The Fifth Affiliated Hospital of Nantong University  Taizhou Jiangsu Province 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