Novel spastic ataxia of Charlevoix-Saguenay gene compound heterozygous mutations in late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay
10.3760/cma.j.issn.1006-7876.2017.11.007
- VernacularTitle:新发复合杂合突变导致迟发型常染色体隐性遗传性痉挛性共济失调Charlevoix-Saguenay型
- Author:
Wei SUN
1
;
Meng YU
;
Yongjie ZHUO
;
Zhaoxia WANG
;
Yun YUAN
Author Information
1. 100034,北京大学第一医院神经内科
- Keywords:
Spinocerebellar degenerations;
Ataxia;
Polyneuropathies;
Magnetic resonance imaging;
Mutation
- From:
Chinese Journal of Neurology
2017;50(11):831-836
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical features and laboratory results in a patient with late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay ( ARSACS ) carrying novel SACS ( spastic ataxia of Charlevoix-Saguenay ) gene heterozygous mutations .Methods A 26-year-old Chinese man developed since the age of 13 a progressive weakness and stiffness of his bilateral lower limbs and gait unsteadiness.He had pyramidal tract sign in his bilateral lower limbs , cerebellar ataxia and sensory-motor polyneuropathy , with hyperelastica and swan neck-like deformities of the fingers , pes cavus and hammer toes.Funduscopy and optical coherence tomography , brain and cervical MRI , conduction velocity of peripheral nerve , motor evoked potentials , visual and brainstem auditory evoked potentials , ultrasound of peripheral nerve , hips and legs MRI , electronystagmography , and targeted capture and next generation sequencing were performed .Results Funduscopy and optical coherence tomography revealed thickening of the retinal nerve fiber layer with unclear margined optic disc .MRI revealed symmetrical linear hypointensity lesions in the pons on T 2 and T2 FLAIR weighted images , thickened bilateral cerebellar peduncles , and flattened and atrophied cervical and upper thoracic spinal cord .Nerve conduction studies showed sensory nerve action potentials were absent in four limbs , motor conduction velocity was slowed , amplitude of muscle response was significantly decreased in lower-limb nerves ( decreased by 80% -100%) but normal in upper-limb nerves.Central motor conduction time of motor evoked potential was prolonged .Targeted capture and next generation sequencing revealed novel SACS compound heterozygous mutations , c.12637 _12638delGA (p.Glu4213ArgFs*3) and c.11274_11276delAAC (p.Ile3758_Thr3759delinsMet) derived from each parent respectively , which were confirmed by Sanger sequencing analyses . Conclusions Recognizing ARSACS triad and its characteristics on fundus and brain MRI is helpful for correct diagnosis . Our findings expand the clinical and genetic spectrum of ARSACS .
