Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Department of Respiratory Medicine, Diagnosis and Treatment Center of Respiratory Disease, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
Biomed Res Int. 2021 Jan 11;2021:4381272. doi: 10.1155/2021/4381272. eCollection 2021.
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 () 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.
瓦登伯格综合征（WS）是一组罕见的遗传性疾病，其特征为听力损失、毛发、皮肤和眼睛颜色改变，以及面部形态改变。提茨综合征是另一种罕见的疾病，其表现型与 WS 相似。提茨/瓦登伯格综合征患者常表现为淡蓝色眼睛、白化病皮肤和独特的毛发颜色，如白发斑或过早变灰的毛发。目前，超过六个候选基因负责四种类型的瓦登伯格综合征和提茨综合征。本研究旨在鉴定一个有听力损失、蓝灰色虹膜、白化病皮肤和白发的三代汉族家庭的致病基因突变。为了发现导致疾病表型的分子遗传病变，对来自中国河北的一个汉族提茨/瓦登伯格综合征表型先证者进行了全外显子组测序。在一个中国汉族的提茨/瓦登伯格综合征家系中发现了一个新的杂合 c.650G>C/p.Arg217Thr 变异。Sanger 测序进一步验证了该突变存在于 3 名受影响个体中，而不存在于健康家庭成员中。生物信息学分析预测该突变是有害的。本研究进一步确定了该家系的遗传病变。同时，我们的研究也可能有助于遗传咨询、体外受精胚胎的胚胎筛选以及提茨/瓦登伯格综合征患者的产前基因诊断，特别是对于先证者、未婚未孕的女性，以减少该汉族家系的家族性传播。
