Van Bergen et al. (2020) described a single, potentially pathogenic, homozygous TRAPPC4 (MIM* 610971) splice site variant (NM_016146.6: c.454+3A>G) shared among seven subjects from three unrelated families of different ethnicities. The affected subjects presented with severe intellectual disability, developmental delay, epilepsy, spasticity, dystonia, microcephaly, and facial dysmorphism (neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy; NEDESBA, MIM# 618741). Brain MRI images were characterized by severe cerebral atrophy and relatively milder cerebellar atrophy. The authors described the variant allele as a likely recurrent ‘mutation hotspot’ based on the absence of a shared haplotype among the families. The same variant was subsequently identified in an Indian girl sharing the same neurological phenotype with skeletal muscle involvement (Kaur et al., 2020).

中文翻译：

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发育迟缓和小脑萎缩家系中 TRAPPC4 的双等位基因框内缺失


范伯根等人。 (2020) 描述了来自不同种族的三个不相关家庭的七名受试者共有的单一、潜在致病性、纯合TRAPPC4 (MIM* 610971) 剪接位点变异 (NM_016146.6: c.454+3A>G)。受影响的受试者表现出严重的智力障碍、发育迟缓、癫痫、痉挛、肌张力障碍、小头畸形和面部畸形（伴有癫痫、痉挛和脑萎缩的神经发育障碍；NEDESBA，MIM＃618741）。脑部MRI图像的特点是严重的脑萎缩和相对较轻的小脑萎缩。作者将变异等位基因描述为可能反复出现的“突变热点”，因为家族之间不存在共享的单倍型。随后在一名印度女孩中发现了相同的变异，该女孩具有与骨骼肌受累相同的神经表型（Kaur等，2020）。