BACKGROUND Agenesis of the corpus callosum (ACC) is a relatively common brain malformation in children with developmental disabilities, caused by mutations in many genes. These genetic causes are characterized by their extreme heterogeneity with more than 300 causative genes identified to date. CASE REPORT We describe two new cases from a three-generation family with ACC and a de novo mutation of the sonic hedgehog (SHH) gene. The affected family members had mild intellectual disability, broad forehead, and widely spaced eyes. A next-generation sequencing (NGS) approach revealed a stop-gain mutation (NM_000193.2:c.1300_1301insA p.Trp434Ter) of the SHH gene; it is the first family to report ACC associated with a single SHH gene mutation. CONCLUSION ACC with mild intellectual disability and facial dysmorphism may be caused by a mutation in SHH, but further research investigating the genotype-phenotype correlation of SHH mutations is required.

中文翻译：

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与胼胝体发育不全、轻度智力障碍和面部畸形相关的家族性声波刺猬 (SHH) 停止增益突变

背景胼胝体发育不全（ACC）是发育障碍儿童中一种相对常见的脑畸形，由许多基因突变引起。这些遗传原因的特点是具有极端的异质性，迄今为止已鉴定出 300 多个致病基因。病例报告 我们描述了来自三代家庭的两个新病例，这些病例患有 ACC 和声波刺猬 (SHH) 基因的从头突变。受影响的家庭成员有轻度智力障碍，前额宽阔，双眼间距大。新一代测序 (NGS) 方法揭示了 SHH 基因的停止增益突变 (NM_000193.2:c.1300_1301insA p.Trp434Ter)；它是第一个报告与单个 SHH 基因突变相关的 ACC 的家族。结论 轻度智力障碍和面部畸形的 ACC 可能是由 SHH 突变引起的，