Spinocerebellar Ataxia Type 28 in a Chinese Pedigree: A Case Report and Literature Review

Spinocerebellar ataxia (SCA) is a common neurogenetic disease, which mainly manifests as ataxia of posture, gait and limbs, cerebellar dysarthria, cerebellar and supranuclear eye movement disorders. It is found that SCA is a kind of progressive neurodegenerative disease including many subtypes, which is mainly mapped to two genetic patterns as: autosomal dominant cerebellar ataxia (ADCA) and autosomal recessive cerebellar ataxia (ARCA). Molecular genetic diagnosis functions as a necessity in its clinical diagnosis and treatment. In our previous clinical work, we found a family with ataxia who presented a c.1852A > G missense mutation in the exon region of AFG3L2 gene by whole exome sequencing (WES) and Sanger validation. Spinocerebellar ataxia type 28 (SCA28) was suspected, which was not reported in the previous literature. We here report the case and review the literature.

Spinocerebellar Ataxia 17: A clinical Rubik’s cube

Spinocerebellar ataxia 17 (SCA 17) has been recognized as one of the most heterogeneous forms of autosomal dominant cerebellar ataxia (ADCA), with a wide clinical spectrum at presentation. SCA17 presenting as Huntington disease like-4 (HDL-4) phenotype has been observed only sporadically or in solitary individuals within a family. We report the case of a young Indian male who presented with juvenile Parkinsonism (HDL like phenotype) features without family history subsequently diagnosed as SCA17.

Interpretation of Variants of Uncertain Significance in the Clinical Setting: A Case of Treatable Ataxia

Background: Spinocerebellar ataxia type 38 (SCA38) is an autosomal dominant cerebellar ataxia caused by pathogenic variants in the elongation of very long chain fatty acids-like 5 gene (ELOVL5). Improvement of ataxia with a docosahexaenoic acid (DHA) replacement therapy has been reported.Case presentation: A 73-year-old man of Hispanic descent presented with gait and limb ataxia, dysarthria, slow and hypometric saccades, hearing loss, mild cognitive impairment, and hypopalesthesia. The initial scale for the assessment and rating of ataxia (SARA) score was 11. After a negative routine workout for ataxia and testing for common forms due to expanded repeats, whole-exome sequencing (WES) identified a heterozygous variant (c.327+1G>A) in the ELOVL5 gene that was predicted to have a negative effect on splicing but was categorized as a Variant of Uncertain Significance (VUS). The patient was started on DHA 600 mg/day. Four months later, the patient showed a considerable reduction in the scale for the assessment and rating of ataxia (SARA) score, from 11 to 5 points, with a clear improvement in gait and limb ataxia that was sustained at 24 months of follow-up.Conclusions: We illustrate the case of a patient presenting with a variant considered genetically and biochemically of uncertain significance. Despite being a VUS, its location in a gene that is known to cause ataxia (SCA38), as well as a compatible phenotype, led to the interpretation of this variant as probably pathogenic from a clinical practice standpoint, especially considering prior reports that showed clinical improvement with a specific, over-the-counter, pharmacological treatment. A further satisfactory response to treatment supported our clinical approach.

The dynamic mutation investigation and whole exome sequencing in a cohort of Chinese autosomal dominant cerebellar ataxia patients

Background Spinocerebellar ataxias (SCAs) are the autosomal dominant cerebellar ataxia (ADCA) with great clinical and genetic heterogeneity. Genetic testing will contribute to the final diagnosis. Methods A total of 204 Chinese ADCA patients were recruited and 190 had genetic testing. Dynamic mutations of SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) were screened firstly. For the patients with negative results, the dynamic mutations of HTT of Huntington Disease (HD), SCA31, 36 and even the whole exome sequencing (WES) were further performed. We investigated the genetic results and clinical characteristics retrospectively. Results Among these 190 index cases, 177(93.16%) were identified SCA dynamic mutations. SCA3 was the commonest, accounting for 70.06%, followed by SCA1 (9.6%), 2 (9.05%), 12 (3.39%), 6 (2.26%), DRPLA (2.26%), 7(1.13%), 8 (1.13%) and 17(0.56%). One patient carried a compound dynamic mutation of SCA6 and SCA17 (SCA6/17). No SCA10 or SCA36 was found. Among the remaining 13 patients, three were diagnosed with HD (1.58%) and one with Episodic Ataxia 2 (EA2). WES did reveal several variants with uncertain significance (VUS) in the remaining nine patients, but failed to detect causative mutations. Conclusion We illustrated the approach and challenge of genetic testing in Chinese ADCA patients. Dynamic mutations of SCAs should be screened firstly. When the results were negative, dynamic mutation of HTT would better be screened consequently. In early-onset ADCA patients, WES might be effective to identify causative mutations, but in adult-onset cases, WES might be less effective.

A Patient with Spinocerebellar Ataxia 2 Presenting with Multiple System Atrophy

Spinocerebellar ataxia type-2 (SCA2) is an autosomal dominant cerebellar ataxia that occurs due to expanded CAG trinucleotide repeats in the ATXN2 gene. Clinical features of parkinsonism in SCA2 vary from phenotypes of levodopa-responsive parkinsonism to multiple system atrophy. We described a patient with SCA2 presenting typical clinical manifestations of multiple system atrophy-c type with levodopa responsive parkinsonism whose dopamine transporter (DAT) image showed atypically reduced DAT uptake in in the striatum.