Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures
Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures
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DOI：
10.1007/s00439-016-1726-y
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发表时间：
2016-11-01
期刊：
影响因子：
5.3
通讯作者：
Alkuraya, Fowzan S.
中科院分区：
文献类型：
--
作者：
Tabarki, Brahim;AlMajhad, Nabil;Alkuraya, Fowzan S.
KCNMA 1基因的显性功能获得性突变，编码大电导电压和Ca 2+激活的K+通道的成孔亚基，在少数癫痫、阵发性运动障碍和发育迟缓综合征患者中有报道。在这份报告中，我们描述了这种新描述的疾病基因的功能丧失表型。在一个患有癫痫、发育迟缓和严重小脑萎缩的近亲家族的两个兄弟姐妹中，联合外显子组/自体染色体组分析在两个孩子中鉴定出KCNMA 1的纯合移码重复（c.2026dupT; p.（Tyr 676 Leufs（*）7））。我们的报告定义了一种新的常染色体隐性KCNMA 1相关的癫痫表型，包括小脑萎缩而无阵发性运动障碍，并强调了发育中的大脑对KCNMA 1编码通道活性增加和减少的敏感性。
Dominant gain-of-function mutations of the KCNMA1 gene, encoding the pore-forming subunit of the large conductance voltage- and Ca2+-activated K+ channel, have been described in a few patients with the syndrome of epilepsy, paroxysmal dyskinesias and developmental delay. In this report, we describe the loss-of-function phenotype of this newly described disease gene. In two siblings from a consanguineous family with epilepsy, developmental delay and severe cerebellar atrophy, combined exome/autozygome analysis identified a homozygous frameshift duplication in KCNMA1 (c.2026dupT; p. (Tyr676 Leufs(*)7)) in both children. Our report defines a novel autosomal recessive KCNMA1-related epileptic phenotype that encompasses cerebellar atrophy without paroxysmal dyskinesia, and highlights the sensitivity of the developing brain to both increased and decreased activity of the KCNMA1-encoded channels.