1. A novel homozygous truncating variant of NECAP1 in early infantile epileptic encephalopathy: the second case report of EIEE21
- Author
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Satomi Mitsuhashi, Atsushi Takata, Lip H Moey, Takeshi Mizuguchi, Mitsuko Nakashima, Satoko Miyatake, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto, Gaik S Ch'ng, and Teik-Beng Khoo
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Ohtahara syndrome ,Nonsense mutation ,030105 genetics & heredity ,Biology ,Epileptogenesis ,03 medical and health sciences ,Adaptor Protein Complex alpha Subunits ,Seizures ,Internal medicine ,Complementary DNA ,Genetics ,medicine ,Humans ,Synaptic vesicle recycling ,Genetics (clinical) ,Messenger RNA ,Homozygote ,Brain ,Infant ,medicine.disease ,Burst suppression ,030104 developmental biology ,Endocrinology ,Mutation ,RNA splicing ,Spasms, Infantile - Abstract
We report the second case of early infantile epileptic encephalopathy (EIEE) arising from a homozygous truncating variant of NECAP1. The boy developed infantile-onset tonic-clonic and tonic seizures, then spasms in clusters. His electroencephalogram (EEG) showed a burst suppression pattern, leading to the diagnosis of Ohtahara syndrome. Whole-exome sequencing revealed the canonical splice-site variant (c.301 + 1 G > A) in NECAP1. In rodents, Necap1 protein is enriched in neuronal clathrin-coated vesicles and modulates synaptic vesicle recycling. cDNA analysis confirmed abnormal splicing that produced early truncating mRNA. There has been only one previous report of a mutation in NECAP1 in a family with EIEE; this was a nonsense mutation (p.R48*) that was cited as EIEE21. Decreased mRNA levels and the loss of the WXXF motif in both the families suggests that loss of NECAP1 function is a common pathomechanism for EIEE21. This study provided additional support that synaptic vesicle recycling plays a key role in epileptogenesis.
- Published
- 2019
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