Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family

Shiroh Miura, Hiroki Shibata, Hiroshi Kida, Kazuhito Noda, Takayuki Toyama, Naoka Iwasaki, Akiko Iwaki, Mitsuyoshi Ayabe, Hisamichi Aizawa, Takayuki Taniwaki, Yasuyuki Fukumaki

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)


    Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant hereditary SPG caused by mutations in the SPAST gene. We studied the four-generation pedigree of a Japanese family with autosomal dominant hereditary SPG both clinically and genetically. Twelve available family members (ten affected; two unaffected) and two spouses were enrolled in the study. The clinical features were hyperreflexia in all four limbs, spasticity of the lower extremities, impaired vibration sense, mild cognitive impairment confirmed by the Wechsler Adult Intelligence Scale-Third Edition, and peripheral neuropathy confirmed by neurophysiological examinations. All four female patients experienced miscarriages. The cerebrospinal fluid tau levels were mildly increased in two of three patients examined. Linkage analyses revealed the highest logarithm of odds score of 2.64 at 2p23-p21 where the SPAST gene is located. Mutation scanning of the entire exonic regions of the SPAST gene by direct sequencing revealed no mutations. Exonic copy number analysis by real-time quantitative polymerase chain reaction revealed heterozygous deletion of exons 1 to 4 of the SPAST gene. Breakpoint analysis showed that the centromeric breakpoint was located within intron 4 of SPAST while the telomeric breakpoint was located within intron 3 of the neighboring DPY30 gene, causing a deletion of approximately 70 kb ranging from exons 1 to 3 of DPY30 to exons 1 to 4 of SPAST. To our knowledge, this is the first report of SPG4 associated with partial deletions of both the SPAST and DPY30 genes. The partial heterozygous deletion of DPY30 could modify the phenotypic expression of SPG4 patients with this pedigree.

    Original languageEnglish
    Pages (from-to)25-31
    Number of pages7
    Issue number1
    Publication statusPublished - Feb 2011

    All Science Journal Classification (ASJC) codes

    • Genetics
    • Genetics(clinical)
    • Cellular and Molecular Neuroscience


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