Niu Wenxia, Xu Huijuan, Qin Litao, Wang Guangke, Ding Shaoguang, Xie Cuncun, Jia Xiaodong, Liu Hongjian
Department of Otolaryngology Head and Neck Surgery，Henan University People's Hospital，Henan Provincial People's Hospital，Zhengzhou，450003，China.
Henan Provincial People's Hospital，Zhengzhou University People's Hospital，Medical Genetics of Henan Provincial.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 Feb;35(2):131-136. doi: 10.13201/j.issn.2096-7993.2021.02.009.
The aim of this study is to analyze the mutation characteristics of GJB2 and SLC26A4 gene in patients with delayed non-syndromic hearing loss, which is beneficial to the early detection and intervention of delayed deafness. Sanger sequencing technology was used to detect two common genes in 139 patients with non-syndromic deafness, six hot spot mutations in GJB2 gene and SLC26A4 gene, and single heterozygous mutations found in GJB2 gene and SLC26A4 gene were detected by whole exome sequencing. Among the 25 patients with deafness caused by GJB2 gene mutation, 12 of them passed universal newborn hearing screening and then developed delayed extremely severe hearing loss. The onset time of hearing loss was 6-48 months. All the genotypes were homozygous or compound heterozygous mutation of c. 235delC, especially genotype of GJB2 c. 235delC homozygous and c. 235delC/c. 299-300 delAT compound heterozygous mutations, and the CT manifestations were normal. Among the 42 patients with deafness caused by SLC26A4 gene mutation, 30 of them passed universal newborn hearing screening and developed delayed deafness. The onset time of hearing loss was three months to ten years old. Among them, the genotypes of 21 patients were compound heterozygous mutation, and 9 patients were homozygous mutation of c. 919-2A>G, especially genotypes were SLC26A4 c. 919-2A>G/c. 665G>T and c. 919-2A>G /c. 2027T>A compound heterozygous mutation. The CT findings of 19 cases showed single enlarged vestibular aqueduct, and 11 cases showed enlarged vestibular aqueduct with Mondini malformation. For the children who have passed universal newborn hearing screening, the genotypes detected are GJB2 c. 235delC homozygous, SLC26A4 c. 919-2A>G homozygous or compound heterozygous mutations, especially genotypes GJB2 c. 235delC homozygous, c. 235delC/c. 299-300delAT compound heterozygous mutations and SLC26A4 c. 919-2A>G/c. 665G>T and c. 919-2A>G/c. 2027T>A compound heterozygous mutation. Attention should be paid to the hearing problems of children all the time, and the possibility of delayed deafness in the future should be considered.
本研究旨在分析非综合征型迟发性听力损失患者中GJB2和SLC26A4基因的突变特征，这有利于迟发性耳聋的早期发现和干预。采用桑格测序技术检测139例非综合征型耳聋患者中的两个常见基因、GJB2基因和SLC26A4基因的六个热点突变，并通过全外显子组测序检测GJB2基因和SLC26A4基因中发现的单杂合突变。在25例由GJB2基因突变引起耳聋的患者中，有12例通过了新生儿听力普遍筛查，随后发展为迟发性极重度听力损失。听力损失的发病时间为6 - 48个月。所有基因型均为c. 235delC的纯合或复合杂合突变，尤其是GJB2 c. 235delC纯合子和c. 235delC/c. 299 - 300 delAT复合杂合突变，CT表现正常。在42例由SLC26A4基因突变引起耳聋的患者中，有30例通过了新生儿听力普遍筛查并发展为迟发性耳聋。听力损失的发病时间为3个月至10岁。其中，21例患者的基因型为复合杂合突变，9例患者为c. 919 - 2A>G纯合突变，尤其是基因型为SLC26A4 c. 919 - 2A>G/c. 665G>T和c. 919 - 2A>G /c. 2027T>A复合杂合突变。19例患者的CT表现为单个前庭导水管扩大，11例表现为前庭导水管扩大合并Mondini畸形。对于已通过新生儿听力普遍筛查的儿童，检测到的基因型为GJB2 c. 235delC纯合子、SLC26A4 c. 919 - 2A>G纯合子或复合杂合突变，尤其是基因型GJB2 c. 235delC纯合子、c. 235delC/c. 299 - 300delAT复合杂合突变以及SLC26A4 c. 919 - 2A>G/c. 665G>T和c. 919 - 2A>G/c. 2027T>A复合杂合突变。应始终关注儿童的听力问题，并考虑未来迟发性耳聋的可能性。
