Ionic currents were recorded with an EPC-10 (HEKA Elektronik, Lambrecht, Germany). of the patient, and to our knowledge, this is actually the first report of successful differentiation from the patient-derived iPSCs into Purkinje cells. There was no significant difference in the differentiation status between control- and patient-derived iPSCs. == Findings == To date, several channel genes have been reported because causative genes for SCA. Our findings provide important insights into the pathogenesis of SCA as a channelopathy. == Electronic supplementary material == The online edition of this article (doi: 10. 1186/s13041-015-0180-4) contains supplementary material, which is available to certified users. Keywords: Spinocerebellar ataxia, CACNA1G, T-type calcium channel, CaV3. 1, Induced pluripotent stem cell == Background == Spinocerebellar ataxia (SCA) is characterized by cerebellar ataxia, dysarthria, oculomotor disorder, extrapyramidal sign, motor neuron sign, epilepsy, cognitive impairment, and many other symptoms [1]. To date, 36 loci have been shown to be involved in autosomal dominant SCA, and the causative genes and mutations have been identified intended for 31 types of SCAs [2]. The majority of SCAs account for replicate expansion, including a coding CAG repeat (SCA13, 6, 7, 17, and dentatorubral-pallidoluysian atrophy) causing misfolding of the encoded TSHR protein due to the expanded polyglutamine tracts; groups of noncoding CAG, CTG, ATTCT, and GGCCTG repeats (SCA8, 10, 12, and 36); and large TGGAA repeat insertions (SCA31) that induce RNA-mediated gain-of-function mechanisms. The remaining known SCA types are caused by single nucleotide variants or indels (SCA5, 11, 1315, 1821, 23, 2628, 34, 35, 38, 40, and 41) in genes that encode various functional proteins [2]. CACNA1A(MIM 601011) was first reported as a causative gene of SCA6 (MIM 183086) among the genes encoding channels [3, 4]. In recent years, potassium channel mutations have been explained in SCA13 (MIM 605259) and SCA19/22 (MIM 607346) [57]. Episodic ataxia (EA) is one of the diseases associated with SCA, and some types of EA are caused by FB23-2 mutations in calcium channel. CACNA1AandCACNB4mutations lead to EA2 (MIM 108500) and EA5 (MIM 613855), respectively [8, 9]. Thus the ion channel dysfunction plays a vital role in the pathogenesis of ataxia and related diseases. We have been engaged in clinicogenetic study using the samples from more than 2, 000 patients with SCA. From a thorough examination of the disease types and the geographical distributions from the FB23-2 2, 121 patients, causative genes intended for 26. 6 % from the dominant-inherited cases (205 out of 721) are still unfamiliar [10]. Therefore , in order to identify book causative genes, we applied exome sequencing to the family members with dominantly inherited SCA. == Methods == == Patients == We enrolled two Japanese families with segregating dominating traits intended for cerebellar ataxia. There are 10 affected individuals in the family 1 and five in the family members 2 . Blood samples were obtained from eight affected individuals and three unaffected individuals in family members 1, and five affected individuals and two unaffected individuals in family members 2 (Fig. 1a). Almost all patients were diagnosed with SCA by neurologists. Prior to this study, we confirmed that affected individuals had no pathogenic mutations causing SCA13, 6, 8, and dentatorubral-pallidoluysian atrophy. The study was approved by the Human Subjects Committees of Hiroshima University; almost all subjects provided written knowledgeable consent. == Fig. 1 . == Identification of a mutation inCACNA1Gcausing FB23-2 SCA. aPedigree charts of family members 1 and 2 . Arrows indicate the probands. Packed and open symbols symbolize affected and unaffected individuals, respectively. Genotypes of the variant c. 5144G > A are shown under the number of samples. Asterisks indicate the patients used for exome sequencing. w, cResults of linkage analysis. Arrows indicate the positions ofCACNA1G. dSanger sequencing to confirm theCACNA1Gvariant. The reference nucleotide G is overlapped with variant nucleotide A in the mutant sample. eStructure of CaV3. 1 encoded byCACNA1G. The star indicates the position of the recognized mutation. The mutation was located in the segment 4 (S4) from the fourth replicate. fConservation at the location of the mutation. The nucleotide and protein sequences are completely conserved among vertebrates. gHaplotype analysis. From the result of SNP genotyping, the haplotypes of both families around theCACNA1Ggene coincided for 360 kb == Linkage analysis == The samples used for linkage analysis were 1-III-2, 1-III-4, 1-III-6, 1-III-8, 1-III-11, 1-III-13, 1-IV-2, 1-IV-3, and 1-IV-4. Because it was possible that 1-IV-3 and 1-IV-4 did not reach the appropriate age at onset, both samples were treated because unknown in the pedigree file of linkage analysis. Genomic DNA (gDNA) was extracted from the peripheral lymphocytes from the participants in accordance to standard protocols. We used a Genome-Wide Human being SNP Array 6. 0 (Affymetrix, Santa Clara, CA, USA) intended for.