期刊
NEUROLOGY
卷 79, 期 21, 页码 2115-2121出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182752c5a
关键词
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资金
- Medical Research Council (MRC)
- Wellcome Trust
- Muscular Dystrophy Campaign, Action Medical Research
- Dystonia Medical Research Foundation (DMRF)
- National Organisation for Rare Disorders (NORD)
- Brain Research Trust (BRT)
- Italian Ministry of Health
- Reta Lila Weston Fellowship
- Robert Bosch Fellowship
- National Institute for Health Research (NIHR) UCLH/UCL Comprehensive Biomedical Research Centre
- MRC [G0802158, G108/638, G1001253, MC_PC_09003, G0802760, MC_G1000735, G0801316, G116/147, G0200373, MC_G0901330] Funding Source: UKRI
- Action Medical Research [1722, 1725] Funding Source: researchfish
- Medical Research Council [G1001253, G116/147, G0200373, MC_G1000735, G0801316, G0802158, MC_G0901330, G0802760, G108/638, MC_PC_09003] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10376] Funding Source: researchfish
Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. Neurology (R) 2012;79:2115-2121
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