Daud Shakeela, Kakar Naseebullah, Goebel Ingrid, Hashmi Abu Saeed, Yaqub Tahir, Nürnberg Gudrun, Nürnberg Peter, Morris-Rosendahl Deborah J, Wasim Muhammad, Volk Alexander E, Kubisch Christian, Ahmad Jamil, Borck Guntram
a Institute of Biochemistry and Biotechnology (IBBt), UVAS , Lahore , Pakistan .
b Institute of Human Genetics, University of Ulm , Ulm , Germany .
Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(3-4):260-5. doi: 10.3109/21678421.2015.1125501. Epub 2016 Jan 11.
Biallelic mutations of ALS2 cause a clinical spectrum of overlapping autosomal recessive neurodegenerative disorders: infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (ALS2). We report on eleven individuals affected with IAHSP from two consanguineous Pakistani families. A combination of linkage analysis with homozygosity mapping and targeted sequencing identified two novel ALS2 mutations, a c.194T > C (p.Phe65Ser) missense substitution located in the first RCC-like domain of ALS2/alsin and a c.2998delA (p.Ile1000*) nonsense mutation. This study of extended families including a total of eleven affected individuals suggests that a given ALS2 mutation may lead to a phenotype with remarkable intrafamilial clinical homogeneity.
ALS2的双等位基因突变会导致一系列临床症状重叠的常染色体隐性神经退行性疾病：婴儿期起病的上行性遗传性痉挛性截瘫（IAHSP）、青少年原发性侧索硬化症（JPLS）和青少年肌萎缩侧索硬化症（ALS2）。我们报告了来自两个巴基斯坦近亲家庭的11名患有IAHSP的个体。通过连锁分析与纯合性定位以及靶向测序相结合，鉴定出两个新的ALS2突变，一个是位于ALS2/alsin第一个RCC样结构域的c.194T＞C（p.Phe65Ser）错义替代，另一个是c.2998delA（p.Ile1000*）无义突变。这项对包括总共11名受影响个体的大家庭的研究表明，特定的ALS2突变可能导致家族内临床同质性显著的表型。
