A novel nonsense autosomal dominant mutation in the GLRA1 gene causing hyperekplexia

被引：0
作者：
Ivan Milenkovic
Alexander Zimprich
Martin Gencik
Kirsten Platho-Elwischger
Stefan Seidel
机构：
[1] Medical University of Vienna,Department of Neurology
[2] Human Genetic Lab,undefined
[3] Rehabilitation Center Meidling,undefined
来源：
Journal of Neural Transmission | 2018年 / 125卷
关键词：
Clobazam; Drug holiday; GLRA1; Hyperekplexia; Startle;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
We present a family with two members affected by hyperekplexia and two unaffected members. All exons in the glycine receptor alpha 1 subunit gene (GLRA1) were sequenced in all four family members. Our index patient harbored a novel nonsense mutation (p.Trp314*; rs867618642) in the transmembrane domain three of the GLRA1 and a novel missense variant in the NH2-terminal part (p.Val67Met; rs142888296). After development of tolerance for the effective treatment with clobazam a drug holiday led to a sustained restoration of the treatment response.
引用
收藏
页码：1877 / 1883
页数：6
相关论文
共 147 条
  • [1] Andermann F(1980)Startle disease or hyperekplexia: further delineation of the syndrome Brain 103 985-997
  • [2] Keene DL(2002)Openings of the rat recombinant alpha 1 homomeric glycine receptor as a function of the number of agonist molecules bound J Gen Physiol 119 443-466
  • [3] Andermann E(2008)The novel hyperekplexia allele GLRA1(S267N) affects the ethanol site of the glycine receptor Eur J Hum Genet 16 223-228
  • [4] Quesney LF(2007)Hyperekplexia caused by dominant-negative suppression of glyra1 function Neurology 68 1947-1949
  • [5] Beato M(2014)The impact of human hyperekplexia mutations on glycine receptor structure and function Mol Brain 7 2-33759
  • [6] Groot-Kormelink PJ(2013)New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms J Biol Chem 288 33745-9620
  • [7] Colquhoun D(2010)Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia J Neurosci 30 9612-876
  • [8] Sivilotti LG(2001)A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia Eur J Hum Genet 9 873-436
  • [9] Becker K(1996)Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis J Med Genet 33 435-1645
  • [10] Breitinger HG(2007)A novel GLRA1 mutation in a recessive hyperekplexia pedigree Mov Disord 22 1643-155
12345678910