Introduction
The spinocerebellar ataxia (SCA) is a group of autosomal dominant genetic disorders showing progressive ataxia, loss of balance, and/or incoordination. Approximately fifty types of SCA have been reported and their corresponding genes have been identified. However, the exact causative genes of several SCAs such as SCA 4, 18, 20, and 30 have not yet been determined, but only the related loci are known. Here, we report a case of cerebellar atrophy with 1.4 Mb deletion on chromosome 4q34.3, which is suspected as SCA 30.
Case:
A 20-year-old male was referred to the neuromuscular disease clinic because of gait ataxia, abnormal ocular motilities, and mild dysarthria. On examination, motor and sensory test were normal. In the cerebellar function test, the finger-to-nose test and rapid alternating movements of the hands were slow and inaccurate. When conducting tandem gait, slight sway was seen. On neuro-ophthalmologic examination, the levator excursion function assessment to examine ptosis showed abnormalities with less than 10mm elevation in both sides (normal: > 15mm). The ocular excursion test showed vertical gaze limitation and painful horizontal excursion. In the saccade test, slow and hypometric saccade with delayed latency was revealed. The horizontal saccade was more impaired than the vertical saccade. The smooth pursuit was impaired in all directions and convergence was impaired without nystagmus.
Brain MRI and orbit CT revealed atrophy of superior cerebellar vermis with non-specific findings of orbits, extraocular muscles, and optic nerves (Fig. 1A, 1B). The patient was performed genetic tests including the targeted gene sequencing panel related with inherited ataxia and the tests of short tandem repeat sequences expansions for SCA 1, 2, 3, 6, 8, and 12, showed non-diagnostic results. Array comparative genomic hybridization analysis revealed a segment deletion of 1.4Mb within chromosome 4q34.3 (179516838_180901085). In the parents’ test, the same deletion was identified in the mother with mild dysarthria and ataxia (Fig. 2A).
Discussion
SCA30 was first reported and named in 2009. The region of chromosome 4q34.3-35.1 (5.0Mb) was suggested as the corresponding locus through the genome-wide linkage analysis at that time. This is the second report and the more narrowed copy number variation on chromosome 4q34.3 (179514388_180917782) was identified compared to the previous report (1.4Mb vs 5.0Mb). Our case has similar characteristics including slow evolving ataxia, atrophy of superior cerebellar vermis, abnormal ocular motilities, dysarthria, and autosomal dominant pattern. The evidence presented above suggests that the new narrowed region of chromosome 4q34.3 can be the corresponding locus for SCA 30. Interestingly, there are no known protein-coding genes on the region of chromosome 4q34.3 (179514388_180917782) (Fig 2B). Further studies are needed to learn more information about SCA30 and molecular cause.
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Figure 1. (A) Brain magnetic resonance image showed superior cerebellar vermis atrophy. (B) Orbit computed tomography revealed non-specific findings of orbits, extraocular muscles, and optic nerves.
(A) Single nucleotide polymorphism array analysis of chromosome 4 from the proband (top), his mother (middle), and his father (bottom). Breakpoints were demonstrated on arr[GRCh37] 4q34.3 (179514388_180917782) deletion in the proband and his mother. (B) The deletion was estimated to be 1.4Mb in size. There are no known protein-cording genes on the region of 4q34.3 (179514388_180917782) (https://grch37.ensembl.org/Homo_sapiens/).
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