Objective: To study the phenotype and genotype variability of CACNA1A in a cohort of ataxia.

Background: CACNA1A gene encodes a voltage-dependent, P/Q type calcium channel which plays a key role in generating and transmitting electrical signal in neurons. Its mutations can cause multiple different phenotypes like spinocerebellar ataxia type 6, episodic ataxia type 2 or familial hemiplegic migraine.

Methods: We recruited 4 patients from 3 Taiwanese families with episodic ataxia. The genetic analysis of CACNA1A was carried out by candidate next generation sequencing and was confirmed by Sanger sequencing.

Results: Three novel missense mutations of CACNA1A gene were identified in our families. They had common phenotype in episodic unsteady gait. The first family had mutation in exon 19: c.2978A>T, p.Glu993Val (Family I, 1 patient) with age at onset (AAO) about 17 years old. The patient had mixed fine and jerky tremor at head and trunk. The second family had mutation in exon 10: c.1265G>A, p.Arg422Gln (Family II, 1 patient) with AAO about 19 years old. The patient had nystagmus, slurring speech, action tremor and jerky tremor. The third family had mutation in exon 27: c.4537G>T, p.Arg1437Leu (Family III, 2 patients) with AAO about 30 years old. The frequency of episodic ataxia was about 3 times per month and duration about 30 minutes. The patient III-2 had tinnitus, gaze evoked nystagmus and mild ataxia. Both Family II and III also had sensory peripheral neuropathy. The neuroimaging study in Family I and III revealed cerebellar and brain stem atrophy. There were no seizure or headache in these patients.

Conclusions: We had shown various phenotypes in three novel mutations of CACNA1A in a cohort of Taiwanese.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotype-and-genotype-variability-of-cacna1a-in-a-cohort-of-ataxia-in-taiwan/