SACS基因突变与Charlevoix-Saguenay病(ARSACS)的常染色体隐性遗传性痉挛性共济失调或Charcot-Marie-Tooth病(CMT)的复杂临床表型有关。这项研究旨在通过全外显子组测序(WES)鉴定韩国CMT队列中的SACS突变。因此,4个家族中的8个致病性SACS突变被确定为这些复杂表型的根本原因.具有SACS突变的CMT家族的患病率确定为0.3%。所有的病人都有感觉,电机,和步态障碍与深肌腱反射增加。对四名患者进行了下肢磁共振成像(MRI),所有患者均进行了脂肪置换。值得注意的是,他们在下肢近端和远端肌肉之间都有类似的脂肪浸润,与大多数无SACS突变且有远端显性脂肪受累的CMT患者的神经肌肉影像学特征不同.因此,这些发现被认为是具有SACS突变的CMT患者的特征性特征.尽管需要对更多病例进行进一步研究,我们的结果突出了SACS突变的CMT患者的下肢MRI表现,拓宽了临床范围.我们建议在具有共济失调和痉挛的复杂表型的隐性CMT患者中筛查SACS。
Mutations in the
SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This
study aimed to identify
SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic
SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with
SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with
SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.