Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, PR China.
Department of Otolaryngology-Head and Neck Surgery, Maternal and Child Health Hospital of Gansu Province, Lanzhou, Gansu, China.
Mol Genet Genomic Med. 2024 Feb;12(2):e2361. doi: 10.1002/mgg3.2361.
We aimed to evaluate the genotype-phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA).
We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next-generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing.
Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919-2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6.
The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants.
评估 2 名中国前庭导水管扩大（EVA）患者的基因型-表型关系。
收集每个家系成员的血样和临床数据。采用标准方法从外周血白细胞中提取基因组 DNA。对该家系进行靶向二代测序和 Sanger 测序，以寻找致病突变。采用微基因试验验证新型内含子突变 SLC26A4c.765+4A>G 是否影响 mRNA 剪接。
通过听觉测试和影像学检查诊断 EVA 患者的听力损失。在 SLC26A4 中检测到两个致病性突变 c.765+4A>G 和 c.919-2A>G。体外微基因分析证实 c.765+4A>G 变异可导致外显子 6 跳跃，从而导致异常剪接。
SLC26A4c.765+4A>G 突变是中国 EVA 家系的致病突变。应特别注意内含子变异。
