期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
卷 188, 期 9, 页码 2712-2717出版社
WILEY
DOI: 10.1002/ajmg.a.62878
关键词
anarthria; dystonia; ENTPD1; hereditary spastic paraplegias; SPG64
Hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive gait impairment and lower extremity spasticity. There are more than 80 defined types of HSP. Genetic testing and imaging results are crucial for diagnosis.
Hereditary spastic paraplegias (HSP) are a group of inherited, neurodegenerative disorders characterized by progressive gait impairment, lower extremity spasticity and increased patellar reflexes. More than 80 types of HSP have been defined to date. In complicated forms, lower limb spasticity and gait impairment is accompanied by an additional neurological finding. Autosomal recessive (AR) HSPs are usually identified in complicated forms and occur more frequently in countries where consanguineous marriage is more widespread. Next generation sequencing techniques, developed in the last decade, have led to the identification of many new types of HSP and reduced the diagnostic odyssey. Whole exome sequencing (WES) can diagnose up to 75% of undiagnosed HSP patients. Targeted genetic analysis with good clinical phenotyping gives the best diagnostic yields for rare diseases. Clinical heterogeneity is prominent in AR complicated HSP. However, some clinical features complicating the disease or magnetic resonance imaging findings, including thin corpus callosum or white matter abnormalities, can help to distinguish some types. AR spastic paraplegia type 64 (SPG64) is a very rare HSP, caused by a mutation in the ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) gene, first described in 2014. To date only nine patients from five families have been reported. We present two siblings with a novel pathogenic variant in ENTPD1, diagnosed by WES, as the sixth published family. We propose that early onset in childhood, cognitive impairment, dysarthria/anarthria, dystonia and areflexia may be the distinctive features of SPG64 and more clinical evidence from families with pathogenic ENTPD1 variants is warranted.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据