Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions.
10.1007/s11684-021-0863-4
- Author:
Yulan CHEN
1
;
Dianfu CHEN
1
;
Shaoyun ZHAO
1
;
Gonglu LIU
2
;
Hongfu LI
3
;
Zhi-Ying WU
4
Author Information
1. Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310009, China.
2. Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
3. Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310009, China. hongfuli@zju.edu.cn.
4. Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310009, China. zhiyingwu@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
PRRT2;
infantile convulsions;
paroxysmal kinesigenic dyskinesia;
penetrance
- MeSH:
Dystonia;
Epilepsy, Benign Neonatal/genetics*;
Humans;
Membrane Proteins/genetics*;
Mutation;
Nerve Tissue Proteins/genetics*;
Pedigree;
Penetrance;
Seizures/genetics*
- From:
Frontiers of Medicine
2021;15(6):877-886
- CountryChina
- Language:English
-
Abstract:
Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP) PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers. PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5%-80.7%) in relatives and 74.5% (95% CI 70.2%-78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%, P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%, P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.
