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...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.CASE SUMMARY 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 lateonset 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.CONCLUSION 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.展开更多
·AIM: To identify the pathogenic mutations in a Chinese pedigree affected with Usher syndrome type II(USH2).· METHODS: The ophthalmic examinations and audiometric tests were performed to ascertain the phenot...·AIM: To identify the pathogenic mutations in a Chinese pedigree affected with Usher syndrome type II(USH2).· METHODS: The ophthalmic examinations and audiometric tests were performed to ascertain the phenotype of the family. To detect the genetic defect,exons of 103 known RDs-associated genes including 12 Usher syndrome(USH) genes of the proband were captured and sequencing analysis was performed to exclude known genetic defects and find potential pathogenic mutations. Subsequently, candidate mutations were validated in his pedigree and 100 normal controls using polymerase chain reaction(PCR) and Sanger sequencing.·RESULTS: The patient in the family occurred hearing loss(HL) and retinitis pigmentosa(RP) without vestibular dysfunction, which were consistent with standards of classification for USH2. He carried the compound heterozygous mutations, c.721 C 】T and c.1969 C 】T, in the MYO7 A gene and the unaffected members carried only one of the two mutations. The mutations were not present in the 100 normal controls.· CONCLUSION: We suggested that the compound heterozygous mutations of the MYO7 A could lead to USH2, which had revealed distinguished clinical phenotypes associated with MYO7 A and expanded the spectrum of clinical phenotypes of the MYO7 A mutations.展开更多
目的探讨Usher综合征1型(Usher syndrome type 1,USH1)相关基因在136例中国河南籍耳聋家庭中的变异情况。方法总结2016年11月至2019年12月在郑州大学第一附属医院遗传与产前诊断中心应用二代测序(next-generation sequencing,NGS)技术...目的探讨Usher综合征1型(Usher syndrome type 1,USH1)相关基因在136例中国河南籍耳聋家庭中的变异情况。方法总结2016年11月至2019年12月在郑州大学第一附属医院遗传与产前诊断中心应用二代测序(next-generation sequencing,NGS)技术进行耳聋基因检测的136个耳聋家庭的临床资料和测序数据,统计分析USH1相关基因(MYO7A、USH1C、CDH23、PCDH15、USH1G、CIB2)的变异情况。结果共有5个耳聋家庭检测到USH1相关基因的9个致病或可能致病变异,占所有耳聋家庭的3.7%(5/136),其中4个耳聋家庭致病基因为MYO7A,1个耳聋家庭致病基因为CDH23,9个变异中的7个变异为首次报道,包括MYO7A基因的c.313delG、c.5257dupA、c.5435A>T、c.5636G>C、c.5722T>G变异,以及CDH23基因的c.155166del、c.4802delA变异。其中家庭2和家庭3的患者视力目前无异常,但根据基因诊断及行走延迟考虑为USH1的可能性大。结论在本组河南籍耳聋患者中,MYO7A为USH1相关基因中最常见的致病基因。应用NGS技术可以在视觉症状出现之前对USH1患者进行初步诊断。展开更多
文摘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.CASE SUMMARY 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 lateonset 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.CONCLUSION 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.
基金Supported by the Postdoctoral Science Foundation of China(No.2014M562542)
文摘·AIM: To identify the pathogenic mutations in a Chinese pedigree affected with Usher syndrome type II(USH2).· METHODS: The ophthalmic examinations and audiometric tests were performed to ascertain the phenotype of the family. To detect the genetic defect,exons of 103 known RDs-associated genes including 12 Usher syndrome(USH) genes of the proband were captured and sequencing analysis was performed to exclude known genetic defects and find potential pathogenic mutations. Subsequently, candidate mutations were validated in his pedigree and 100 normal controls using polymerase chain reaction(PCR) and Sanger sequencing.·RESULTS: The patient in the family occurred hearing loss(HL) and retinitis pigmentosa(RP) without vestibular dysfunction, which were consistent with standards of classification for USH2. He carried the compound heterozygous mutations, c.721 C 】T and c.1969 C 】T, in the MYO7 A gene and the unaffected members carried only one of the two mutations. The mutations were not present in the 100 normal controls.· CONCLUSION: We suggested that the compound heterozygous mutations of the MYO7 A could lead to USH2, which had revealed distinguished clinical phenotypes associated with MYO7 A and expanded the spectrum of clinical phenotypes of the MYO7 A mutations.
文摘目的探讨Usher综合征1型(Usher syndrome type 1,USH1)相关基因在136例中国河南籍耳聋家庭中的变异情况。方法总结2016年11月至2019年12月在郑州大学第一附属医院遗传与产前诊断中心应用二代测序(next-generation sequencing,NGS)技术进行耳聋基因检测的136个耳聋家庭的临床资料和测序数据,统计分析USH1相关基因(MYO7A、USH1C、CDH23、PCDH15、USH1G、CIB2)的变异情况。结果共有5个耳聋家庭检测到USH1相关基因的9个致病或可能致病变异,占所有耳聋家庭的3.7%(5/136),其中4个耳聋家庭致病基因为MYO7A,1个耳聋家庭致病基因为CDH23,9个变异中的7个变异为首次报道,包括MYO7A基因的c.313delG、c.5257dupA、c.5435A>T、c.5636G>C、c.5722T>G变异,以及CDH23基因的c.155166del、c.4802delA变异。其中家庭2和家庭3的患者视力目前无异常,但根据基因诊断及行走延迟考虑为USH1的可能性大。结论在本组河南籍耳聋患者中,MYO7A为USH1相关基因中最常见的致病基因。应用NGS技术可以在视觉症状出现之前对USH1患者进行初步诊断。
