Department of Radiology, Capital Institute of Pediatrics, Beijing 100020 PR China.
Department of Medical Genetics, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020 PR China.
Brain Dev. 2020 Nov;42(10):771-774. doi: 10.1016/j.braindev.2020.07.004. Epub 2020 Jul 21.
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.
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.
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.
胼胝体发育不全（ACC）是一种在发育障碍儿童中相对常见的脑畸形，由许多基因的突变引起。这些遗传病因具有极高的异质性，迄今为止已确定了超过 300 个致病基因。
我们描述了一个具有 ACC 和 sonic hedgehog（SHH）基因新发突变的三代家族中的两个新病例。受影响的家族成员有轻度智力障碍、宽额头和眼睛间距宽。下一代测序（NGS）方法揭示了 SHH 基因的一个无义突变（NM_000193.2：c.1300_1301insA p.Trp434Ter）；这是第一个报道与单个 SHH 基因突变相关的 ACC 家族。
伴有轻度智力障碍和面部畸形的 ACC 可能由 SHH 基因突变引起，但需要进一步研究调查 SHH 突变的基因型-表型相关性。
