Dystrophia canthorum in Waardenburg syndrome with a novel MITF mutation

AIM: To reveal a novel MITF gene mutation in Waardenburg syndrome (WS), which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes, hair and skin.METHODS: The genetic analysis of the Chinese family was conducted by whole-exome sequencing, then the results were confirmed by Sanger sequencing.RESULTS: WS is classified into type I to IV, which are identified by the W index, clinical characteristics and additional features. The MITF gene mostly accounts for WS type II. In this study, a de novo heterozygous mutation in the MITF gene, c.638A>G in exon 7, was identified in the patient diagnosed with WS type I features, as the W index was 2.17 (over 2.10), with dystrophia canthorum, congenital bilateral profound hearing loss, bilateral heterochromia irides, premature greying of the hair, and excessive freckling on the face at birth. She also underwent refractive errors and esotropia, reduced pigmentation of the choroid and visible choroid vessels. The mutation was not found in previous studies or mutation databases.CONCLUSION: The novel mutation in the MITF gene, which altered the protein in amino acids 213 from the glutamic acid to glycine, is the genetic pathological cause for WS features in the patient. Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS, which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities. Moreover, ocular symptoms should be emphasized in all types of WS patients.

目的：揭示瓦登伯格综合征（WS）中一种新的MITF基因突变。WS是一种常染色体显性遗传性神经源性疾病，包括不同程度的感音神经性耳聋以及眼睛、头发和皮肤的色素异常。 方法：通过全外显子组测序对中国的一个家系进行基因分析，然后用桑格测序法对结果进行验证。 结果：WS分为I - IV型，通过W指数、临床特征和其他特征来鉴别。MITF基因主要与II型WS有关。在本研究中，在一名被诊断具有I型WS特征的患者中发现了MITF基因的一个从头杂合突变，即外显子7的c.638A>G，该患者的W指数为2.17（大于2.10），伴有内眦赘皮、先天性双侧极重度听力损失、双侧虹膜异色、头发早白以及出生时面部有过多雀斑。她还存在屈光不正和内斜视、脉络膜色素减少以及可见脉络膜血管。该突变在以往的研究或突变数据库中未被发现。 结论：MITF基因的这种新突变使第213位氨基酸从谷氨酸变为甘氨酸，是该患者出现WS特征的遗传病理原因。这个家系的这些特征揭示了WS中MITF的一种新的遗传异质性，扩充了MITF突变数据库，并为校正不同种族中WS的W指数值提供了可能。此外，在所有类型的WS患者中都应强调眼部症状。