Association of Early-Onset Spasticity and Risk for Cognitive Impairment With Mutations at Amino Acid 499 in SPAST
Association of Early-Onset Spasticity and Risk for Cognitive Impairment With Mutations at Amino Acid 499 in SPAST
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DOI：
10.1177/0883073818756680
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发表时间：
2018-04-01
影响因子：
1.9
通讯作者：
Boycott, Kym M.
中科院分区：
文献类型：
--
作者：
Gillespie, Meredith K.;Humphreys, Peter;Boycott, Kym M.
遗传性痉挛性截瘫是一种表型和遗传异质性的神经退行性疾病，其特征是下肢无力和痉挛。痉挛性截瘫4 （SPG4）是由SPAST基因的杂合突变引起的，通常在受影响的个体中引起迟发性、简单形式的遗传性痉挛性截瘫。SPG4的其他临床特征偶有报道，但尚未建立基因型与表型的相关性。通过针对性的临床检测，我们发现了2例无亲缘关系的女性患者，他们在SPAST中具有相同的p.a g499his从头突变。两名患者均表现为早发性痉挛，导致运动里程碑延迟，这导致一名儿童被诊断为脑瘫，另一名儿童被诊断为脊髓栓系。回顾文献发现了几个氨基酸499突变的患者和与认知障碍风险相关的早发症状。早期和准确的诊断儿童早发性痉挛是重要的知情预后和遗传咨询。
Hereditary spastic paraplegia is a phenotypically and genetically heterogeneous group of neurodegenerative disorders characterized by lower extremity weakness and spasticity. Spastic paraplegia 4 (SPG4), caused by heterozygous mutations in the gene SPAST, typically causes a late-onset, uncomplicated form of hereditary spastic paraplegia in affected individuals. Additional clinical features in SPG4 have been reported on occasion, but no genotype-phenotype correlation has been established. Through targeted clinical testing, we identified 2 unrelated female patients with the same de novo p.Arg499His mutation in SPAST. Both patients presented with early-onset spasticity resulting in delayed motor milestones, which led to a diagnosis of cerebral palsy in one child and tethered cord in the other. Review of the literature identified several patients with mutations at amino acid 499 and early-onset symptoms associated with a risk of cognitive impairment. Early and accurate diagnosis of children with early-onset spasticity is important for informed prognosis and genetic counselling.