一个POU4F3基因变异所致常染色体显性聋15型家系的遗传学分析
Genetic Analysis of a Pedigree with Autosomal Dominant Deafness Type 15 Caused by POU4F3 Gene Variation
丁仲军;毛宝宏;张钏;倪亚莉;王肃旸;许文婧;王译萱;苟芳丽;刘青
1:甘肃中医药大学第一临床医学院
2:甘肃省妇幼保健院
摘要【Abstract] Objective To clarify the possible genetic etiology by carrying out a genetic analysis on a family with non-syndromic autosomal dominant progressive hearing loss. Methods Genetic analysis was carried out in the proband using whole-exome sequencing， and the suspected pathogenic sites were verified by Sanger sequencing and detected in family members. Results A heterozygous variant was detected in POU4F3 c. 337C>T (p. Q113 * ) related to non-syndromic autosomal dominant deafness type 15 (DFNA15) in the proband. This heterozygous variant was detected in other 5 patients (Ⅱ-2，Ⅲ-2，Ⅲ-4，Ⅲ-5 and ⅢI-7) in this family, but the variant was not found in 4 cases(Ⅲ-1，Ⅲ-3，Ⅲ-6 and IV-2) with normal hearing. The pathogenicity of this variant was rated according to the relevant guidelines of the American College of Medical Genetics and Genomics (ACMG). The evidence of the variant was PVS1 + PM2 + PP1, which was a pathogenic variant. Conclusion This family is a rare family with DFNA15caused by heterozygous variation of POU4F3 gene, and there may be genetic anticipation. The c. 337C>T(p. Q113 *) variant in POU4F3 gene is the genetic etiology of deafness in this family, which can provide a basis for genetic counseling in this family.
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