PDF(Pubmed)
Abstract：
BACKGROUND: Variants in the MYO7A gene commonly result in Usher syndrome, and in rare cases lead to autosomal dominant non-syndromic deafness (DFNA11). Currently, only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical. Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family.
METHODS: The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss. We learned from the patient\'s medical history collection that multiple family members also had similar hearing loss, generally occurring around the age of 40. Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant. To provide evidence supporting that this variant is responsible for the hearing loss in the studied family, we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype. In addition, the clinical manifestation of the 11 affected family members was found to be late-onset bilateral slowly progressive hearing loss, inherited in this family in an autosomal dominant manner. None of the affected family members had visual impairment or vestibular symptoms; therefore, we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.
CONCLUSIONS: We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants, and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.
METHODS: The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss. We learned from the patient\'s medical history collection that multiple family members also had similar hearing loss, generally occurring around the age of 40. Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant. To provide evidence supporting that this variant is responsible for the hearing loss in the studied family, we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype. In addition, the clinical manifestation of the 11 affected family members was found to be late-onset bilateral slowly progressive hearing loss, inherited in this family in an autosomal dominant manner. None of the affected family members had visual impairment or vestibular symptoms; therefore, we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.
CONCLUSIONS: We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants, and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.
摘要：
背景：MYO7A基因的变异通常会导致Usher综合征，在极少数情况下导致常染色体显性遗传的非综合征性耳聋（DFNA11）。目前,据报道,只有9种变异体与DFNA11相关,且其临床表型并不相同.在这里，我们提出了在三代中国家族中鉴定出的导致DFNA11的新变体。
方法：先证者是一名53岁的汉族男性，他表现为舌后双侧对称中度感音神经性听力损失。我们从患者的病史收集中了解到，多个家庭成员也有类似的听力损失，一般发生在40岁左右。随后通过高通量测序进行的研究鉴定了一种新的MYO7A变体。为了提供证据证明这种变异是导致所研究家庭听力损失的原因，我们对11个家族成员进行了Sanger测序,发现变异体与耳聋表型共分离.此外,11名受累家庭成员的临床表现为迟发性双侧缓慢进行性听力损失，以常染色体显性遗传的方式在这个家庭中遗传。受影响的家庭成员没有视力障碍或前庭症状；因此，我们认为，这种新颖的MYO7A变体是该家族中罕见的DFNA11的原因。
结论：我们报告了一个新的变体，导致DFNA11，它进一步丰富了MYO7A变体的集合，我们对先前已确定的引起DFNA11的9种变体的回顾为临床遗传咨询提供了参考。
方法：先证者是一名53岁的汉族男性，他表现为舌后双侧对称中度感音神经性听力损失。我们从患者的病史收集中了解到，多个家庭成员也有类似的听力损失，一般发生在40岁左右。随后通过高通量测序进行的研究鉴定了一种新的MYO7A变体。为了提供证据证明这种变异是导致所研究家庭听力损失的原因，我们对11个家族成员进行了Sanger测序,发现变异体与耳聋表型共分离.此外,11名受累家庭成员的临床表现为迟发性双侧缓慢进行性听力损失，以常染色体显性遗传的方式在这个家庭中遗传。受影响的家庭成员没有视力障碍或前庭症状；因此，我们认为，这种新颖的MYO7A变体是该家族中罕见的DFNA11的原因。
结论：我们报告了一个新的变体，导致DFNA11，它进一步丰富了MYO7A变体的集合，我们对先前已确定的引起DFNA11的9种变体的回顾为临床遗传咨询提供了参考。
