Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Neurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India.
Ann Hum Genet. 2022 Mar;86(2):94-101. doi: 10.1111/ahg.12452. Epub 2021 Dec 8.
TRAPPC4-related neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (MIM# 618741) is a recently described TRAPPopathy with clinical findings of developmental delay, seizures, postnatal microcephaly, spasticity, facial dysmorphism, and cerebral and cerebellar atrophy. Muscle involvement, a frequent finding in TRAPPopathies, was observed in one individual with TRAPPC4-related disorder previously. Only a single variant, an in-frame deletion in one family has been reported outside a recurrent disease-causing variant. We report three individuals from two Indian families harboring novel bi-allelic missense variants c.191T>C and c.278C>T (NM_016146.6) in TRAPPC4 with classic clinical presentation in one and milder and later onset in the other family. We provide further evidence for muscle involvement and review the detailed phenotypic findings in individuals reported with this disorder till date.
TRAPPC4 相关的神经发育障碍伴癫痫、痉挛和脑萎缩（MIM# 618741）是一种最近描述的 TRAPP 病，其临床特征为发育迟缓、癫痫发作、出生后脑小畸形、痉挛、面畸形以及大脑和小脑萎缩。TRAPP 病中常发现肌肉受累，此前曾在一位 TRAPPC4 相关疾病患者中观察到。除了一种复发性致病变异外，仅在一个家族中报告了一种单一的框内缺失变异。我们报告了来自两个印度家族的三个人，他们携带 TRAPPC4 中的新型双等位基因错义变异 c.191T>C 和 c.278C>T（NM_016146.6），其中一个家族具有典型的临床表现，另一个家族的临床表现则较轻微且发病较晚。我们提供了肌肉受累的进一步证据，并回顾了迄今为止报道的该疾病患者的详细表型发现。
