Nonsense mutations of SMC1A gene cause early onset epilepsy limited to females with cluster seizures: response to ketogenic diet add-on therapy
- Author:
Chunhui Hu
1
,
2
;
Deying Liu
3
,
4
,
5
;
Kan Xiao
6
;
Shuizhen Zhou
1
,
2
;
Yi Wang
1
,
2
;
Dan Sun
7
,
8
,
9
;
Zhisheng Liu
7
,
8
,
9
Author Information
- Publication Type:Journal Article
- Keywords: SMC1A; early onset epilepsy; female with cluster seizures; ketogenic diet
- From:Neurology Asia 2021;26(1):55-62
- CountryMalaysia
- Language:English
- Abstract: Background & Objective: Nonsense mutations in SMC1A have been reported only in females with cluster seizures, all of whom have been described as drug-resistant epilepsy. Here, we aim to explore the use of ketogenic diet treatment. Methods: The clinical data of female patients with de novo nonsense mutations in SMC1A were collected and analyzed. The clinical data was recruited and analyzed. The peripheral blood of children and their parents was collected. The next generation sequencing was used to find suspected pathogenic mutations and all the confirmed mutations were verified by Sanger sequencing. Results: Three patients with heterozygous de novo mutations in SMC1A gene were reviewed. All patients were females, presenting with seizure onset at age between 2.5 to 11 months old. One patient had mild developmental delay. One had moderate developmental delay. Another had severe developmental retardation. None of the patients had a clinical diagnosis of Cornelia de Lange syndrome. All three patients had prominent clinical features of cluster seizures. All the nonsense mutations were predicted damaging SMC1A protein by PolyPhen-2 HVAR. All the patients were treated with multiple antiepileptic drugs but their seizures remained refractory. When initiated with ketogenic diet, they became seizure free within 3 to 4 weeks. Conclusion: SMC1A nonsense mutations can cause early onset epilepsy only in females with cluster seizures. These patients are characterized by drug-resistant epilepsy, but all our three patients have good effect on ketogenic diet add-on therapy.
- Full text:20250724113757694697.2020my0102.pdf
