Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica, GENYO, Granada, Spain.
Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica, GENYO, Granada, Spain; Department of Otolaryngology, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria, ibs.GRANADA, Granada, Spain.
Hear Res. 2021 Sep 15;409:108329. doi: 10.1016/j.heares.2021.108329. Epub 2021 Aug 2.
The MYO7A gene encodes a motor protein with a key role in the organization of stereocilia in auditory and vestibular hair cells. Rare variants in the MYO7A (myosin VIIA) gene may cause autosomal dominant (AD) or autosomal recessive (AR) sensorineural hearing loss (SNHL) accompanied by vestibular dysfunction or retinitis pigmentosa (Usher syndrome type 1B). Familial Meniere's disease (MD) is a rare inner ear syndrome mainly characterized by low-frequency sensorineural hearing loss and episodic vertigo associated with tinnitus. Familial aggregation has been found in 6-8% of sporadic cases, and most of the reported genes were involved in single families. Thus, this study aimed to search for relevant genes not previously linked to familial MD. Through exome sequencing and segregation analysis in 62 MD families, we have found a total of 1 novel and 8 rare heterozygous variants in the MYO7A gene in 9 non-related families. Carriers of rare variants in MYO7A showed autosomal dominant or autosomal recessive SNHL in familial MD. Additionally, some novel and rare variants in other genes involved in the organization of the stereocilia links such as CDH23, PCDH15 or ADGRV1 co-segregated in the same patients. Our findings reveal a co-segregation of rare variants in the MYO7A gene and other structural myosin VIIA binding proteins involved in the tip and ankle links of the hair cell stereocilia. We suggest that recessive digenic inheritance involving these genes could affect the ultrastructure of the stereocilia links in familial MD.
MYO7A 基因编码一种运动蛋白，在听觉和前庭毛细胞的静纤毛组织中起关键作用。MYO7A（肌球蛋白 VIIA）基因的罕见变异可能导致常染色体显性（AD）或常染色体隐性（AR）感觉神经性听力损失（SNHL），并伴有前庭功能障碍或视网膜色素变性（Usher 综合征 1B 型）。家族性梅尼埃病（MD）是一种罕见的内耳综合征，主要特征为低频感觉神经性听力损失和与耳鸣相关的阵发性眩晕。在 6-8%的散发性病例中发现了家族聚集性，大多数报道的基因都涉及单个家族。因此，本研究旨在寻找先前与家族性 MD 无关的相关基因。通过对 62 个 MD 家族进行外显子组测序和分离分析，我们在 9 个非相关家族中发现 MYO7A 基因中共有 1 个新的和 8 个罕见的杂合变异。MYO7A 基因罕见变异的携带者在家族性 MD 中表现为常染色体显性或常染色体隐性 SNHL。此外，其他参与静纤毛结构的基因，如 CDH23、PCDH15 或 ADGRV1 的一些新的和罕见的变异也与同一患者中的变异共分离。我们的研究结果揭示了 MYO7A 基因和其他参与毛细胞静纤毛尖端和足踝连接的结构肌球蛋白 VIIA 结合蛋白的罕见变异在家族性 MD 中的共分离。我们建议这些基因的隐性双基因遗传可能会影响家族性 MD 中静纤毛连接的超微结构。
