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Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment


Hereditary spastic paraplegias (HSPs) are characterized by various inherited disorders in which weakness and spasticity of the lower extremities are the predominant symptoms. Recently, HSP caused by ALDH18A1 mutations has been reported as SPG9 with autosomal dominant (SPG9A) and autosomal recessive (SPG9B) transmission. In this study, we obtained clinical and genetic findings in two Japanese families with SPG9B. One family had a novel compound heterozygous mutation (c.1321 C > T/c.1994G > A) in the ALDH18A1 gene. The other family had a homozygous mutation (c.383 G > A/c.383 G > A) in the ALDH18A1 gene. To date, only two SPG9B families with ALDH18A1 mutations have been reported. This is the first report of SPG9 in non-Caucasians. Furthermore, we found cerebellar ataxia in one family, although cerebellar ataxia has not been reported in SPG9B so far. SPG9B might involve a complicated HSP including cerebellar ataxia and cognitive impairment. This study expands the clinical and genetic spectrum of ALDH18A1-related disorders.

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We thank the participants and cooperating doctors in the Japan Spastic Paraplegia Research Consortium (JASPAC). This work was supported by Grants-in-Aid from the Research Committee for Ataxic Disease (Y.T.), the Ministry of Health, Labor and Welfare, Japan, JSPS KAKENHI Grant Number JP17K17772 (K.K.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and grants for AMED under Grant Numbers JP17ek0109078 (Y.T.), JP16kk0205001h0001 (S.T.), and JP17kk0205001h0002 (S.T.).

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Correspondence to Yoshihisa Takiyama.

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The authors declare that they have no conflict of interest.

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Accession Numbers: The nucleotide sequence data reported are available in the GenBank. database under the accession numbers: MH155295, MH155296, MH155297, MH155298, MH155299, MH155300, MH155301, and MH155302.

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Koh, K., Ishiura, H., Beppu, M. et al. Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment. J Hum Genet 63, 1009–1013 (2018).

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