Abstract：
Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient\'s mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. 18F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.
摘要：
UBQLN2基因的变异与一组具有X连锁显性遗传和肌萎缩侧索硬化症（ALS）和/或额颞叶痴呆（FTD）的临床表型的疾病有关。UBQLN2变异的病例在世界范围内很少报告。报道的病例表现出强烈的临床异质性。这里,我们报告了2例汉族成人发病的UBQLN2变异病例。全外显子组测序显示半合子P506S（c.1516C>T）和杂合P509S变异（c.1525C>T），两者都位于热点突变区域内。具有P506S变异的患者是24岁男性。临床特征为痉挛性截瘫，无下运动神经元损伤。患者的母亲是无症状的杂合子携带者，具有偏斜的X染色体失活。具有P509S变异的患者是一名63岁的女性。临床特征包括ALS和帕金森病。18F-荧光多巴PET-CT显示双侧后部壳核突触前多巴胺能缺陷。这些病例进一步突出了UBQLN2病例的临床异质性。
