SPTAN1 encephalopathy: distinct phenotypes and genotypes

被引:62
作者
Tohyama, Jun [1 ,2 ]
Nakashima, Mitsuko [3 ]
Nabatame, Shin [4 ]
Gaik-Siew, Ch'ng [5 ]
Miyata, Rie [6 ]
Rener-Primec, Zvonka [7 ]
Kato, Mitsuhiro [8 ]
Matsumoto, Naomichi [3 ]
Saitsu, Hirotomo [3 ]
机构
[1] Nishi Niigata Chuo Natl Hosp, Dept Child Neurol, Niigata 9502085, Japan
[2] Niigata Univ Med & Dent Hosp, Niigata, Japan
[3] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 232, Japan
[4] Osaka Univ, Grad Sch Med, Dept Pediat, Osaka, Japan
[5] Kuala Lumpur Hosp, Dept Genet, Kuala Lumpur, Malaysia
[6] Tokyo Kita Social Insurance Hosp, Dept Pediat, Tokyo, Japan
[7] Univ Childrens Hosp, Dept Pediat Neurol, Ljubljana, Slovenia
[8] Yamagata Univ, Fac Med, Dept Pediat, Yamagata 990, Japan
基金
日本学术振兴会;
关键词
DE-NOVO MUTATIONS; ALPHA-II-SPECTRIN; INFANTILE EPILEPTIC ENCEPHALOPATHY; ONSET WEST-SYNDROME; INTELLECTUAL DISABILITY; SUPPRESSION-BURST; STXBP1; MUTATIONS; CEREBRAL HYPOMYELINATION; POLYALANINE EXPANSION; CLINICAL SPECTRUM;
D O I
10.1038/jhg.2015.5
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Recent progress in genetic analysis reveals that a significant proportion of cryptogenic epileptic encephalopathies are single-gene disorders. Mutations in numerous genes for early-onset epileptic encephalopathies have been rapidly identified, including in SPTAN1, which encodes alpha-II spectrin. The aim of this review is to delineate SPTAN1 encephalopathy as a distinct clinical syndrome. To date, a total of seven epileptic patients with four different in-frame SPTAN1 mutations have been identified. The major clinical features of SPTAN1 mutations include epileptic encephalopathy with hypsarrhythmia, no visual attention, acquired microcephaly, spastic quadriplegia and severe intellectual disability. Brainstem and cerebellar atrophy and cerebral hypomyelination, as observed by magnetic resonance imaging, are specific hallmarks of this condition. A milder variant is characterized by generalized epilepsy with pontocerebellar atrophy. Only in-frame SPTAN1 mutations in the last two spectrin repeats in the C-terminal region lead to dominant negative effects and these specific phenotypes. The last two spectrin repeats are required for alpha/beta spectrin heterodimer associations and the mutations can alter heterodimer formation between the two spectrins. From these data we suggest that SPTAN1 encephalopathy is a distinct clinical syndrome owing to specific SPTAN1 mutations. It is important that this syndrome is recognized by pediatric neurologists to enable proper diagnostic work-up for patients.
引用
收藏
页码:167 / 173
页数:7
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