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Genotypes and phenotypes of DNM1 encephalopathy

Authors
 Jeehyun Kim  ;  Lip-Yuen Teng  ;  Bilal Shaker  ;  Dokyun Na  ;  Hyun Yong Koh  ;  Soon Sung Kwon  ;  Joon Soo Lee  ;  Heung Dong Kim  ;  Hoon-Chul Kang  ;  Se Hee Kim 
Citation
 JOURNAL OF MEDICAL GENETICS : epub, 2023-05 
Journal Title
JOURNAL OF MEDICAL GENETICS
ISSN
 0022-2593 
Issue Date
2023-05
Keywords
child health ; developmental ; epilepsy
Abstract
Background: Variants in the dynamin-1 (DNM1) gene typically cause synaptopathy, leading to developmental and epileptic encephalopathy (DEE). We aimed to determine the genotypic and phenotypic spectrum of DNM1 encephalopathy beyond DEE.

Methods: Electroclinical phenotyping and genotyping of patients with a DNM1 variant were conducted for patients undergoing next-generation sequencing at our centre, followed by a systematic review.

Results: Six patients with heterozygous DNM1 variants were identified in our cohort. Three had a typical DEE phenotype characterised by epileptic spasms, tonic seizures and severe-to-profound intellectual disability with pathogenic variants located in the GTPase or middle domain. The other three patients had atypical phenotypes of milder cognitive impairment and focal epilepsy. Genotypically, two patients with atypical phenotypes had variants located in the GTPase domain, while the third patient had a novel variant (p.M648R) in the linker region between pleckstrin homology and GTPase effector domains. The third patient with an atypical phenotype showed normal development until he developed febrile status epilepticus. Our systematic review on 55 reported cases revealed that those with GTPase or middle domain variants had more severe intellectual disability (p<0.001) and lower functional levels of ambulation (p=0.001) or speech and language (p<0.001) than the rest.

Conclusion: DNM1-related phenotypes encompass a wide spectrum of epilepsy and neurodevelopmental disorders, with specific variants underlying different phenotypes.
Full Text
https://jmg.bmj.com/content/early/2023/05/28/jmg-2023-109233
DOI
10.1136/jmg-2023-109233
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hoon Chul(강훈철) ORCID logo https://orcid.org/0000-0002-3659-8847
Kwon, Sun Sung(권순성)
Kim, Se Hee(김세희) ORCID logo https://orcid.org/0000-0001-7773-1942
Kim, Heung Dong(김흥동) ORCID logo https://orcid.org/0000-0002-8031-7336
Lee, Joon Soo(이준수) ORCID logo https://orcid.org/0000-0001-9036-9343
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196027
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