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Review
. 2018 Sep;97(36):e12148.
doi: 10.1097/MD.0000000000012148.

A case of a novel CACNA1G mutation from a Chinese family with SCA42: A case report and literature review

Xinyuan Li  1 , Chunkui Zhou, Li Cui, Lijun Zhu, Heqian Du, Jing Liu, Chenglin Wang, Shaokuan Fang
Affiliations
Review

A case of a novel CACNA1G mutation from a Chinese family with SCA42: A case report and literature review

Xinyuan Li et al. Medicine (Baltimore). 2018 Sep.

Abstract

Rationale: Spinocerebellar ataxia (SCA), a genetically inherited heterogeneous disorder, is characterized by gait ataxia, dysarthria, parkinsonism, choreic movements, dystonia, epilepsy, cognitive and psychiatric symptoms. Spinocerebellar ataxia-42 (SCA42), caused by heterozygous mutation in the calcium channel 1G (CACNA1G) gene, is a rare SCA subtype and the transmission pattern is autosomal dominant inheritance.

Patient concerns: We presented a novel mutation (c.4721T>A; p.Met1574Lys) in 3 patients from a Chinese family using whole-exome sequencing. All patients exhibited cerebellar ataxia and the clinical manifestations were similar to those that were previously reported in the French and Japanese families. In addition, cerebral magnetic resonance imaging (MRI) showed cerebellar atrophy, and the hot cross bun sign of brainstem was found in the proband and her sister.

Diagnoses: The clinical features and MRI findings indicated the diagnosis of SCA. Taken together, the symptoms, MRI findings, as well as whole-exome sequencing made the diagnosis of SCA42 most likely candidate.

Interventions and outcomes: The patient was treated with cobamamide (1.5 mg once daily) for nerve nutrition and further physical therapy. At the 4-month follow-up visit, the patient's condition did not improve obviously.

Lessons: Recently, a missense mutation in CACNA1G gene (c.5144G4A; p.Arg1715His) was identified in French and Japanese families with SCA42. However, there has been no report of SCA42 or its mutant loci in Chinese patients. Our finding showed a novel mutation in CACNA1G gene and provided important insights into the pathogenesis of SCA42.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Magnetic resonance imaging (MRI) scans of the brain. Panels (A) and (C) show T2-weighted MRI of the patient (IV-3) brain, panel (B) shows T2-weighted MRI of the patient's sister (IV-2), while panel (D) represents the T2-weighted MRI of the patient's father (III-4).
Figure 2
Figure 2
Pedigree analysis of the patient's family. Black circles (female) and squares (male) indicate family members affected with the disease, while open circles or squares indicate unaffected members. Asterisks indicate the patients used for exome sequencing. Arrows indicate the proband. MRI = magnetic resonance imaging.
Figure 3
Figure 3
Sequencing analysis of the CACNA1G gene locus. Panel (A) shows the genetic profile of the patient (IV-3). Panel (B) represents the genetic profile of the patient's father (III-4), while panel (C) corresponds to the genetic profile of the patient's sister (IV-2). Panel (D) depicts the genetic profile of a family member not affected with the disease (IV-1).
See this image and copyright information in PMC

References

    1. Durr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol 2010;9:885–94. - PubMed
    1. Kimura M, Yabe I, Hama Y, et al. SCA42 mutation analysis in a case series of Japanese patients with spinocerebellar ataxia. J Hum Genet 2017;11. - PubMed
    1. Calhoun JD, Hawkins NA, Zachwieja NJ, et al. Cacna1 g is a genetic modifier of epilepsy in a mouse model of Dravet syndrome. Epilepsia 2017;58:e111–5. - PMC - PubMed
    1. Morino H, Matsuda Y, Muguruma K, et al. A mutation in the low voltage-gated calcium channel CACNA1G alters the physiologicalproperties of the channel, causing spinocerebellar ataxia. Mol Brain 2015;8:89. - PMC - PubMed
    1. Coutelier M, Blesneac I, Monteil A, et al. A recurrent mutation in CACNA1G alters Cav3.1 T-Type calcium-channel conduction and causes autosomal-dominant cerebellar ataxia. Am J Hum Genet 2015;97:726–37. - PMC - PubMed

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