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病例报告：中国一名患者的调控域内出现一种新的截短突变，导致严重的发育性和癫痫性脑病。

Case report: A novel truncating mutation within the regulatory domain causes severe developmental and epileptic encephalopathy in a Chinese patient.

作者信息

Li Jieling, Cao Jie

机构信息

Department of Medical General Ward, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China.

Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Neurol. 2022 Sep 7;13:889167. doi: 10.3389/fneur.2022.889167. eCollection 2022.

DOI:10.3389/fneur.2022.889167
PMID:36158964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9491239/
Abstract

INTRODUCTION

Developmental and epileptic encephalopathy 91 (DEE91; OMIM#617711) is a severe neurodevelopmental disorder caused by heterozygous variants. To the best of our knowledge, only a few DEE91 cases have been reported.

RESULTS

This study reports a boy who experienced recurrent afebrile convulsions and spasms at the age of 2 months. After being given multiple antiepileptic treatments with levetiracetam, adrenocorticotropic hormone (ACTH), prednisone, topiramate, and clonazepam, his seizures were not completely relieved. At the age of 4 months, the patient exhibited delayed neuromotor development and difficulty in feeding; at the age of 6 months, he was diagnosed with developmental regression with recurrent spasms and myoclonic seizures that could respond to vigabatrin. At the age of 1 year and 4 months, the patient showed profound global developmental delay (GDD) with intermittent absence seizures. Whole-exome sequencing (WES) identified a novel loss-of-function variant c.1258_1259insAGTG (p. Val420Glufs32) in .

CONCLUSION

This finding expands the genetic spectrum of the gene and reinforces the theory that DEE91-associated truncating variants cluster within a 26-amino acid region in the regulatory domain (RD) of .

摘要

引言

91型发育性癫痫性脑病（DEE91；OMIM#617711）是一种由杂合变异引起的严重神经发育障碍。据我们所知，仅有少数DEE91病例被报道。

结果

本研究报告了一名2个月大时出现反复无热惊厥和痉挛的男孩。在接受了多种抗癫痫治疗，包括左乙拉西坦、促肾上腺皮质激素（ACTH）、泼尼松、托吡酯和氯硝西泮后，其癫痫发作并未完全缓解。4个月大时，该患者出现神经运动发育迟缓及喂养困难；6个月大时，他被诊断为伴有反复痉挛和肌阵挛发作的发育倒退，这些发作对氨己烯酸有反应。1岁4个月时，该患者表现出严重的全面发育迟缓（GDD），伴有间歇性失神发作。全外显子测序（WES）在[具体基因名称未给出]中鉴定出一个新的功能丧失变异c.1258_1259insAGTG（p.Val420Glufs32）。

结论

这一发现扩展了[具体基因名称未给出]基因的遗传谱，并强化了与DEE91相关的截短变异聚集在[具体基因名称未给出]调节域（RD）中一个26个氨基酸区域内的理论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/61ef2de1d27e/fneur-13-889167-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/42a42771c006/fneur-13-889167-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/af9f8b1bfcbb/fneur-13-889167-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/61ef2de1d27e/fneur-13-889167-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/42a42771c006/fneur-13-889167-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/af9f8b1bfcbb/fneur-13-889167-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9a4/9491239/61ef2de1d27e/fneur-13-889167-g0003.jpg

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