Rhim Jung Woo, Kim Dong-Kee, Han Ji Yoon, Park Joonhong
Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea, Seoul, 06591, Republic of Korea.
Heliyon. 2024 Sep 4;10(17):e36717. doi: 10.1016/j.heliyon.2024.e36717. eCollection 2024 Sep 15.
Autosomal recessive non-syndromic deafness-28 (DFNB28; OMIM #609823) specifically refers to prelingual sensorineural hearing loss (SNHL) resulting from homozygous or compound heterozygous mutations in the TRIO- and F-actin-binding protein, gene. In this report, we present a pediatric patient exhibiting novel compound heterozygous deleterious variants in the gene.
The auditory brainstem response result revealed both left- and right-sided deafness with a threshold of 20 dB normal hearing level in the proband. A comprehensive trio whole exome sequencing (WES) using the Celemics G-Mendeliome Whole Exome Sequencing Panel was employed.
The WES analysis revealed compound heterozygous variants in the proband, namely c.1192_1195delCAACinsT/p.Gln398* classified as pathogenic and c.3661C > T/p.Arg1221Trp categorized as a variant of uncertain significance according to American College of Medical Genetics and Genomics guidelines. These variants are considered the most probable cause of the proband's SNHL.
TRIOBP isoforms are predominantly expressed in the inner ear, contributing to the formation of stereocilia rootlets. Further investigations are required to fully understand the phenotypic variability and establish the pathogenicity of the identified variant in relation to the gene and SNHL.
常染色体隐性非综合征性耳聋28型（DFNB28；OMIM #609823）具体指因TRIO-和F-肌动蛋白结合蛋白基因的纯合或复合杂合突变导致的语前感音神经性听力损失（SNHL）。在本报告中，我们介绍了一名儿科患者，其在该基因中表现出新型复合杂合有害变异。
听觉脑干反应结果显示，先证者双侧耳聋，听力阈值为正常听力水平20分贝。采用Celemics G-Mendeliome全外显子测序面板进行全面的三联体全外显子测序（WES）。
WES分析显示先证者存在复合杂合变异，即根据美国医学遗传学与基因组学学会指南，c.1192_1195delCAACinsT/p.Gln398*被分类为致病性变异，c.3661C>T/p.Arg1221Trp被分类为意义未明的变异。这些变异被认为是先证者SNHL的最可能原因。
TRIOBP异构体主要在内耳表达，有助于静纤毛小根的形成。需要进一步研究以充分了解表型变异性，并确定所鉴定变异与该基因和SNHL相关的致病性。
