[一个患非综合征性常染色体显性遗传性耳聋15型的中国家系的基因检测]
[Genetic testing of a Chinese pedigree affected with non-syndromic autosomal dominant deafness 15].
作者信息
Kang Hongfei, Zhao Kaihui, Kong Xiangdong
机构信息
Genetics and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
出版信息
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Jul 10;38(7):639-642. doi: 10.3760/cma.j.cn511374-20200821-00618.
OBJECTIVE
To explore the genetic basis of a Chinese pedigree affected with progressive non-syndromic sensorineural hearing loss.
METHODS
High-throughput DNA sequencing was carried out to analyze 415 genes associated with hereditary deafness in the proband. Sanger sequencing was carried out to verify the suspected variants among her family members.
RESULTS
The proband was found to carry a heterozygous c.842T>A (p.Ile281Asn) variant of the POU4F3 gene. The same variant was found among all other patients from the pedigree including the proband's mother, brother, aunt and maternal grandfather, but not among those with normal hearing. Based on the standards and guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, the c.842T>A(p.Ile281Asn) variant of the POU4F3 gene was predicted as likely pathogenic (PM2+PM5+PP1+PP3+PP4).
CONCLUSION
A Chinese pedigree affected by a rare type autosomal dominant deafness-15 (DFNA15) due to a novel c.842T>A (p.Ile281Asn) variant of the POU4F3 gene was identified. The result has facilitated genetic counseling and risk assessment for the pedigree.
目的
探究一个患有进行性非综合征性感音神经性听力损失的中国家系的遗传基础。
方法
对先证者进行高通量DNA测序，分析415个与遗传性耳聋相关的基因。对其家庭成员进行桑格测序以验证可疑变异。
结果
发现先证者携带POU4F3基因的杂合c.842T>A（p.Ile281Asn）变异。在该家系的所有其他患者中，包括先证者的母亲、兄弟、阿姨和外祖父，均发现了相同的变异，但听力正常者中未发现。根据美国医学遗传学与基因组学学会以及分子病理学协会的标准和指南，POU4F3基因的c.842T>A（p.Ile281Asn）变异被预测为可能致病（PM2+PM5+PP1+PP3+PP4）。
结论
鉴定出一个因POU4F3基因新的c.842T>A（p.Ile281Asn）变异而患罕见的常染色体显性遗传性耳聋15型（DFNA15）的中国家系。该结果有助于对该家系进行遗传咨询和风险评估。
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