Division of Child Neurology, Department of Pediatrics, Nowon Eulji Medical Center, Eulji University, Seoul 01830, Republic of Korea.
Green Cross Genome, Yongin, Gyeonggi 16924, Republic of Korea.
Mol Med Rep. 2018 Jun;17(6):7611-7617. doi: 10.3892/mmr.2018.8837. Epub 2018 Mar 29.
The ACTG1 gene encodes the cytoskeletal protein γ-actin, which functions in non‑muscle cells and is abundant in the auditory hair cells of the cochlea. Autosomal dominant missense mutations in ACTG1 are associated with DFNA20/26, a disorder that is typically characterized by post‑lingual progressive hearing loss. To date, 17 missense mutations in ACTG1 have been reported in 20 families with DFNA20/26. The present study described a small family with autosomal dominant nonsyndromic hearing loss. A novel heterozygous missense mutation, c.94C>T (p.Pro32Ser), in ACTG1 was identified using the TruSight One sequencing panel. Notably, congenital hearing loss in our proband was identified by newborn hearing screening at birth. In silico predictions of protein structure and function indicate that the p.Pro32Ser mutation may result in conformational changes in γ‑actin. The present study expands the understanding of the phenotypic effects of heterozygous missense mutations in the ACTG1 gene. In specific, the present results emphasize that mutations in ACTG1 result in a diverse spectrum of onset ages, including congenital in addition to post‑lingual onset.
ACTG1 基因编码细胞骨架蛋白 γ-肌动蛋白，该蛋白在非肌肉细胞中发挥作用，在耳蜗的听觉毛细胞中含量丰富。ACTG1 中的常染色体显性错义突变与 DFNA20/26 相关，该疾病的特征通常为后天性进行性听力损失。迄今为止，在 20 个具有 DFNA20/26 的家族中已报道了 17 种 ACTG1 错义突变。本研究描述了一个具有常染色体显性非综合征性听力损失的小家族。使用 TruSight One 测序面板鉴定到 ACTG1 中的一个新的杂合错义突变 c.94C>T（p.Pro32Ser）。值得注意的是，我们的先证者的先天性听力损失在出生时通过新生儿听力筛查被发现。蛋白质结构和功能的计算机预测表明，p.Pro32Ser 突变可能导致 γ-肌动蛋白构象的改变。本研究扩展了对 ACTG1 基因中杂合错义突变表型效应的理解。具体而言，本研究结果强调了 ACTG1 突变导致发病年龄的多样性谱，包括后天性和先天性。
