Kaitian Chen1, Ling Zong2, Yuan Zhan1, Xuan Wu1, Min Liu1, Hongyan Jiang3. 1. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China. 2. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China; Department of Otorhinolaryngology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China. 3. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: jhongy@mail.sysu.edu.cn.
Abstract
OBJECTIVE: Waardenburg syndrome is clinically and genetically heterogeneous. The SOX10 mutation related with Waardenburg syndrome type II is rare in Chinese. This study aimed to uncover the genetic causes of Waardenburg syndrome type II in a three-generation family to improve genetic counseling. METHODS: Complete clinical and molecular evaluations were conducted in a three-generation Han Chinese family with Waardenburg syndrome type II. Targeted genetic counseling was provided to this family. RESULTS: We identified a rare heterozygous dominant mutation c.621C>A (p.Y207X) in SOX10 gene in this family. The premature termination codon occurs in exon 4, 27 residues downstream of the carboxyl end of the high mobility group box. Bioinformatics prediction suggested this variant to be disease-causing, probably due to nonsense-mediated mRNA decay. Useful genetic counseling was given to the family for prenatal guidance. CONCLUSION: Identification of a rare dominant heterozygous SOX10 mutation c.621C>A in this family provided an efficient way to understand the causes of Waardenburg syndrome type II and improved genetic counseling.
OBJECTIVE:Waardenburg syndrome is clinically and genetically heterogeneous. The SOX10 mutation related with Waardenburg syndrome type II is rare in Chinese. This study aimed to uncover the genetic causes of Waardenburg syndrome type II in a three-generation family to improve genetic counseling. METHODS: Complete clinical and molecular evaluations were conducted in a three-generation Han Chinese family with Waardenburg syndrome type II. Targeted genetic counseling was provided to this family. RESULTS: We identified a rare heterozygous dominant mutation c.621C>A (p.Y207X) in SOX10 gene in this family. The premature termination codon occurs in exon 4, 27 residues downstream of the carboxyl end of the high mobility group box. Bioinformatics prediction suggested this variant to be disease-causing, probably due to nonsense-mediated mRNA decay. Useful genetic counseling was given to the family for prenatal guidance. CONCLUSION: Identification of a rare dominant heterozygous SOX10 mutation c.621C>A in this family provided an efficient way to understand the causes of Waardenburg syndrome type II and improved genetic counseling.