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Identification of a Premature Termination Mutation in the Proline-Rich Transmembrane Protein 2 Gene in a Chinese Family with Febrile Seizures

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Abstract

Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene (PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene.

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Abbreviations

BFIS:

Benign familial infantile seizures

CAE:

Childhood-absence epilepsy

CPA6 :

The carboxypeptidase A6 gene

EA:

Episodic ataxia

EKD:

Episodic kinesigenic dyskinesia

FS:

Febrile seizures

GABRG2 :

The gamma-aminobutyric acid receptor gamma 2 gene

GLUT1 :

The glucose transporter 1 gene

GPR98 :

The G protein-coupled receptor 98 gene

GTCS:

Generalized tonic-clonic seizures

HCN2 :

The hyperpolarization-activated cyclic nucleotide-gated potassium channel 2 gene

ICCA:

Infantile convulsions with paroxysmal choreoathetosis

IMPA2 :

The myo-inositol monophosphatase 2 gene

PED:

Paroxysmal exercise-induced dyskinesia

PNKD:

Paroxysmal non-kinesigenic dyskinesia

PRRT2 :

The proline-rich transmembrane protein 2 gene

PT:

Paroxysmal torticollis

SCN1A :

The sodium channel neuronal type I alpha subunit gene

SEZ6 :

The seizures related gene 6 gene

SNAP25:

Synaptosomal-associated protein 25-KD

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Acknowledgments

This study was supported by grants 81101339 and 81271921 from National Natural Science Foundation of China, grant 20110162110026 from Research Foundation for the Doctoral Program of Higher Education of China, grant 2011ssxt194 from Graduate Degree Theses Innovation Foundation of Central South University, China.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

    Wen Zheng, Yan Yang, Zhi Song & Hao Deng

  2. Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, 410013, Hunan, China

    Wen Zheng, Xiong Deng, Lamei Yuan, Zhijian Yang & Hao Deng

  3. Department of Neurology, Hunan Children’s Hospital, Changsha, China

    Jie Zhang

  4. BGI-Shenzhen, Shenzhen, China

    Jingjing Xiao & Liping Guan

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  1. Wen Zheng
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  2. Jie Zhang
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  10. Hao Deng
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Correspondence to Hao Deng.

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Zheng, W., Zhang, J., Deng, X. et al. Identification of a Premature Termination Mutation in the Proline-Rich Transmembrane Protein 2 Gene in a Chinese Family with Febrile Seizures. Mol Neurobiol 53, 835–841 (2016). https://doi.org/10.1007/s12035-014-9047-4

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