Kumai Takumi, Nishio Shin-Ya, Moteki Hideaki, Katada Akihiro, Usami Shin-Ichi
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa 078-8510, Japan.
Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Genes (Basel). 2025 Jan 21;16(2):116. doi: 10.3390/genes16020116.
BACKGROUND/OBJECTIVES: The gene is reported to be the causative gene for non-syndromic recessive sensorineural hearing loss and auditory neuropathy spectrum disorder. About 300 variants have been reported, but there have been no reports to date on copy gain variants.
We identified a copy gain variant in the gene through short-read next-generation sequencing analysis from one patient with auditory neuropathy. We also performed long-read next-generation sequencing analysis using the Oxford Nanopore Technologies adaptive sampling procedure.
The four-year-old male carried a duplication of chr2: 26,477,852 to 26,483,106 (a 5254-base duplication including exon 14 to exon 18 of the gene NM_001287489) and a c.5385C>A single nucleotide variant. We also confirmed that these two variants were located in the configuration based on haplotype phasing results using the long-read next-generation sequencing data.
This is the first report of an auditory neuropathy patient with a large duplication variant in the gene. The identified variants were novel, but based on the clinical phenotype of the patient, these variants seem to be the genetic cause of this patient's phenotype. Oxford Nanopore Technologies adaptive sampling is a powerful tool for the analysis of structural variants (particularly for determining the breakpoint and direction) and haplotype phasing.
背景/目的：据报道，该基因是导致非综合征性隐性感音神经性听力损失和听觉神经病谱系障碍的致病基因。已报道约300种变异，但迄今为止尚无关于拷贝数增加变异的报道。
我们通过对一名听觉神经病患者进行短读长下一代测序分析，在该基因中鉴定出一种拷贝数增加变异。我们还使用牛津纳米孔技术的自适应采样程序进行了长读长下一代测序分析。
这名4岁男性携带2号染色体26,477,852至26,483,106区域的重复（一个5254碱基的重复，包括基因NM_001287489的第14外显子至第18外显子）以及一个c.5385C>A单核苷酸变异。我们还根据使用长读长下一代测序数据的单倍型分型结果证实，这两个变异位于该基因结构中。
这是首例报道的该基因存在大片段重复变异的听觉神经病患者。所鉴定的变异是新的，但基于患者的临床表型，这些变异似乎是该患者表型的遗传原因。牛津纳米孔技术的自适应采样是分析结构变异（特别是确定断点和方向）和单倍型分型的有力工具。
