sequencing of a family with flail arm syndrome

Mutations in hnRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare genetic cause of ALS. To further raise early awareness of this variant subtype of ALS, herein, we described a Chinese pedigree with hnRNPA1-related FAS, which showed great clinical variability among the intra-familial members. Detailed clinical evaluations, muscle biopsy, and whole-exome sequencing were performed in the proband. Exome sequencing identified a documented heterozygous variant in hnRNPA1 gene c.1018C>T (p.P340S), which co-segregated with disease in the family, while the proband's daughter was an asymptomatic mutant carrier.

编码异质性核核糖核蛋白A1（heterogeneous nuclear ribonucleoprotein A1, hnRNP A1）的hnRNPA1基因发生突变，是肌萎缩侧索硬化症（ALS）的一类罕见遗传致病原因。为进一步提升临床对该ALS变异亚型的早期认知，本文报道了一个携带hnRNPA1相关FAS的中国家系，该家系内成员间存在显著的临床表型异质性。先证者接受了详细的临床评估、肌肉活检及全外显子组测序。全外显子组测序检出hnRNPA1基因上一个已报道的杂合突变c.1018C>T（p.P340S），该突变在该家系中与疾病共分离，而先证者的女儿为无症状突变携带者。