PDF(Pubmed)
Abstract：
BACKGROUND: Waardenburg syndrome type 2 (WS2) has been reported to be a rare hereditary disorder, which is distinguished by vivid blue eyes, varying degrees of hearing impairment, and abnormal pigment deposition in the skin and hair. Variants in the sex-determining region Y-box containing gene 10 (SOXl0) gene may cause congenital deafness and have been demonstrated to be important during the development of WS2.
METHODS: Complete clinical data of the proband and her family members (her parents and 2 sisters) was collected and physical examinations were performed in the hospital. The laboratory examination including hemoglobin, Coomb\'s test, urine protein, ENA, autoimmune hepatitis-related autoantibodies and ultrasonography were all conducted. We obtained the peripheral blood samples from all the participants and performed whole exome sequencing and sanger sequencing validation.
RESULTS: The present study identified a family of 5 members, and only the proband exhibited typical WS2. Beyond the characteristics of WS2, the proband also manifested absence of puberty. The proband and her younger sister manifested systemic lupus erythematosus (SLE). Whole exome sequencing revealed a de novo variant in the SOX10 gene. The variant c.175 C > T was located in exon 2 of the SOX10 gene, which is anticipated to result in early termination of protein translation.
CONCLUSIONS: The present study is the first to report a case of both WS2 and SLE, and the present findings may provide a new insight into WS2.
METHODS: Complete clinical data of the proband and her family members (her parents and 2 sisters) was collected and physical examinations were performed in the hospital. The laboratory examination including hemoglobin, Coomb\'s test, urine protein, ENA, autoimmune hepatitis-related autoantibodies and ultrasonography were all conducted. We obtained the peripheral blood samples from all the participants and performed whole exome sequencing and sanger sequencing validation.
RESULTS: The present study identified a family of 5 members, and only the proband exhibited typical WS2. Beyond the characteristics of WS2, the proband also manifested absence of puberty. The proband and her younger sister manifested systemic lupus erythematosus (SLE). Whole exome sequencing revealed a de novo variant in the SOX10 gene. The variant c.175 C > T was located in exon 2 of the SOX10 gene, which is anticipated to result in early termination of protein translation.
CONCLUSIONS: The present study is the first to report a case of both WS2 and SLE, and the present findings may provide a new insight into WS2.
摘要：
背景：Waardenburg综合征2型（WS2）已被报道为一种罕见的遗传性疾病，以生动的蓝眼睛为特征，不同程度的听力障碍，皮肤和头发中的色素沉积异常。包含基因10（SOXl0）基因的性别决定区Y-box的变异可能会导致先天性耳聋，并且已被证明在WS2的发展过程中很重要。
方法：收集先证者及其家人（父母和2姐妹）的完整临床资料，并在医院进行体检。实验室检查包括血红蛋白，库姆的测试，尿蛋白,ENA,均进行了自身免疫性肝炎相关自身抗体和超声检查。我们从所有参与者获得了外周血样本，并进行了全外显子组测序和sanger测序验证。
结果：本研究确定了一个由5名成员组成的家族，只有先证者表现出典型的WS2。除了WS2的特征外，先证者还表现出青春期的缺失。先证者和她的妹妹表现为系统性红斑狼疮（SLE）。全外显子组测序揭示了SOX10基因中的从头变体。变异体c.175C>T位于SOX10基因的外显子2,这预计会导致蛋白质翻译的早期终止。
结论：本研究首次报道了WS2和SLE的病例，目前的发现可能为WS2提供了新的见解。
方法：收集先证者及其家人（父母和2姐妹）的完整临床资料，并在医院进行体检。实验室检查包括血红蛋白，库姆的测试，尿蛋白,ENA,均进行了自身免疫性肝炎相关自身抗体和超声检查。我们从所有参与者获得了外周血样本，并进行了全外显子组测序和sanger测序验证。
结果：本研究确定了一个由5名成员组成的家族，只有先证者表现出典型的WS2。除了WS2的特征外，先证者还表现出青春期的缺失。先证者和她的妹妹表现为系统性红斑狼疮（SLE）。全外显子组测序揭示了SOX10基因中的从头变体。变异体c.175C>T位于SOX10基因的外显子2,这预计会导致蛋白质翻译的早期终止。
结论：本研究首次报道了WS2和SLE的病例，目前的发现可能为WS2提供了新的见解。
