MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome.
MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome.
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在一个患有 Tietz/Waardenburg 综合征的汉族家庭中发现 MITF p.Arg217Thr 变体
DOI：
10.1155/2021/4381272
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发表时间：
2021
影响因子：
--
通讯作者：
Fan LL
中科院分区：
文献类型：
--
作者：
Yu R;Liu L;Li YL;Fan LL
Waardenburg综合征（WS）是一组罕见的遗传性疾病，其特征是听力损失，头发，皮肤和眼睛颜色的变化以及面部形状的改变。Tietz综合征是另一种罕见的疾病，表现为与WS相似的表型。Tietz/Waardenburg综合征患者通常表现为淡蓝色眼睛，白化病皮肤和独特的毛发颜色，如一片白色头发或头发过早变灰。目前，超过六个候选基因负责四种类型的Waardenburg综合征和Tietz综合征。本研究旨在鉴定一个三代听力损失、蓝灰色虹膜、白化病皮肤和白色头发的汉族家系的致病基因变异。为了揭示Tietz/Waardenburg综合征的分子遗传学病变，我们对一个中国河北汉族Tietz/Waardenburg综合征家系的先证者进行了全外显子组测序。鉴定了黑素细胞诱导转录因子（MITF）中一种新的杂合c.650G>C/p.Arg217Thr变异体。桑格测序进一步验证了该突变存在于三个患病个体中，而在健康家庭成员中不存在。生物信息学分析预测该突变是有害的。我们的研究进一步确定了该家族的遗传病变。同时，本研究也有助于Tietz/Waardenburg综合征患者的遗传咨询、体外受精胚胎的筛查和产前基因诊断，尤其是对先证者、未婚和未孕妇女，以减少该汉族家系的家族传播。
Waardenburg syndrome (WS) is a group of rare genetic disorders characterized by hearing loss, changes in coloring of hair, skin, and eyes, and alterations in the shape of the face. Tietz syndrome is another rare disorder which presented similar phenotypes to WS. Patients with Tietz/Waardenburg syndrome often present with pale blue eyes, albino skin, and distinctive hair coloring, such as a patch of white hair or hair that prematurely turns gray. At present, more than six candidate genes are responsible for four types of Waardenburg syndrome and Tietz syndrome. This study is aimed at identifying the pathogenic gene variants in a three-generation Han Chinese family with hearing loss, blue-gray iris, albino skin, and white hair. In order to discover the molecular genetic lesion underlying the disease phenotype, whole exome sequencing in the proband, with Tietz/Waardenburg syndrome phenotypes, of a Han Chinese family from HeBei, China, was conducted. A novel heterozygous c.650G>C/p.Arg217Thr variant in melanocyte inducing transcription factor (MITF) was identified. Sanger sequencing further validated that this mutation existed in three affected individuals and absent in healthy family members. Bioinformatics analysis predicted that this mutation was deleterious. Our study further identified the genetic lesion of the family. Simultaneously, our study may also contribute to genetic counseling, embryonic screening of in vitro fertilized embryos, and prenatal genetic diagnosis of patients with Tietz/Waardenburg syndrome, especially for the proband, unmarried and unpregnant women, to reduce familial transmission in this Han Chinese family.
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影响因子：
3.5
作者：
Grill, Christine;Bergsteinsdottir, Kristin;Steingrimsson, Eirikur
通讯作者：
Steingrimsson, Eirikur
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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