Spinocerebellar ataxia type 10 in Chinese Han

History and examination.

The family in this case report lives in a northeastern province of China. The pedigree is noted in the figure, A.

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Figure SCA10 in a Chinese Han family

(A) Pedigree of the Chinese Han spinocerebellar ataxia type 10 (SCA10) family. As best as can be determined, marriages to individuals other than Chinese Han have been excluded. Squares, male; circles, female; black fill, affected; white fill, unaffected; black dot, asymptomatic. Upper left corner, reported age at onset; upper right corner, current age or age at death; lower right corner, pedigree numbering within the generation (asterisk indicates that a genomic DNA sample was obtained); arrow, proband. (B) CT scan of the cerebellum of the mother of the proband (III-2) is indicative of cerebellar atrophy. (C) Southern blot for SCA10 expansion was performed as previously described.⁴ Positive and negative controls are indicated and were run on nonadjacent lanes of the same blot. Calculated expansion sizes are indicated along with pedigree identifiers. (D) Haplotyping analysis of single nucleotide polymorphisms (rs5764850, rs72556348, rs72556349, and rs72556350) flanking the SCA10 expansion in intron 9 of ATXN10 in the Chinese SCA10 family was done as previously described^2,5 and reveals a common haplotype. Red lines, SCA10 chromosome; blue lines, normal chromosome.

SCA10 expansion testing.

Following informed consent and in accordance with institutional review panels at the China-Japan Friendship Hospital, genomic DNA was extracted from peripheral blood leukocytes and tested for the SCA10 expansion by repeat-primed PCR (RP-PCR)⁴ following negative results for SCA1, 2, 3, 6, 7, 8, 12, and 17 and dentatorubral-pallidoluysian atrophy. Further molecular analysis was performed on anonymized samples at the University of Florida after institutional review board approval. The proband (IV-2) tested positive for an SCA10 expansion by RP-PCR, as did her mother (III-2), maternal aunt (III-4), and asymptomatic sister (IV-3). The SCA10 expansion was sized by Southern blot and found to be in the pathogenic range (figure, C). Haplotype analysis showed the “C-expansion-G-G-C” haplotype shared by other SCA10-positive individuals^2,5 (figure, D).

Discussion.

We report SCA10 in a family outside the American continents. The clinical presentation of this family is complex and closely resembles “Mexican” SCA10 (with seizures).¹ The later onset of disease in these individuals is likely a reflection of the short expansion length.^4,6 Absence of cerebellar atrophy in 2 of the individuals is not entirely surprising given their late disease onset and comparatively short expansion allele.

The presence of SCA10 in a Chinese Han family suggests that the original SCA10 mutation may have occurred before the divergence of Proto-Amerinds from ancestral Asians. However, as the shared SCA10 haplotype is relatively common, we cannot rule out alternative hypotheses, including (1) independent expansion events on a common haplotype but in separate geographic locations by chance, or (2) backflow of human migration from Beringia⁷ carrying SCA10 expansions into Asia. While SCA10 may be a rare cause of autosomal dominant cerebellar ataxia in China, the observation of SCA10 in this family suggests that SCA10 should be included in the differential diagnosis of ataxia in patients with Asian origins.