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Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1

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Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive neurodegenerative disorder characterized by retinitis pigmentosa and sensory ataxia. Previous studies of PCARP in two families showed a linkage to 1q31–q32. However, detailed investigations on the clinical presentations as well as molecular genetics of PCARP have been limited. Here, we describe a Japanese consanguineous family with PCARP. Two affected siblings suffered from childhood-onset retinitis pigmentosa and slowly progressive sensory ataxia. They also showed mild mental retardation, which has not been described in patients with PCARP. Parametric linkage analysis using high-density single nucleotide polymorphism arrays supported a linkage to the same locus. Target capture and high-throughput sequencing technologies revealed a novel homozygous c.1477G>C (G493R) mutation in FLVCR1, which cosegregated with the disease. A recent study has identified three independent mutations in FLVCR1 in the original and other families. Our results further confirmed that PCARP is caused by mutations in FLVCR1.

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  1. Higgins JJ, Morton DH, Loveless JM (1999) Posterior column ataxia with retinitis pigmentosa (AXPC1) maps to chromosome 1q31–q32. Neurology 52:146–150

    PubMed  CAS  Google Scholar 

  2. Higgins JJ, Kluetzman K, Berciano J, Combarros O, Loveless JM (2000) Posterior column ataxia and retinitis pigmentosa: a distinct clinical and genetic disorder. Mov Disord 15:575–578

    Article  PubMed  CAS  Google Scholar 

  3. Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, Miyashita A, Kuwano R, Adachi H, Nakamura E, Tsuji S (2009) SNP-HiTLink: a high-throughput linkage analysis system employing dense SNP data. BMC Bioinformatics 10:121

    Article  PubMed  CAS  Google Scholar 

  4. Gudbjartsson DF, Thorvaldsson T, Kong A, Gunnarsson G, Ingolfsdottir A (2005) Allegro version 2. Nat Genet 37:1015–1016

    Article  PubMed  CAS  Google Scholar 

  5. Hodges E, Xuan Z, Balija V, Kramer M, Molla MN, Smith SW, Middle CM, Rodesch MJ, Albert TJ, Hannon GJ, McCombie WR (2007) Genome-wide in situ exon capture for selective resequencing. Nat Genet 39:1522–1527

    Article  PubMed  CAS  Google Scholar 

  6. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25:1754–1760

    Article  PubMed  CAS  Google Scholar 

  7. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R (1000) Genomes Project Data Processing Subgroup (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25:2078–2079

    Article  Google Scholar 

  8. Rajadhyaksha AM, Elemento O, Puffenberger EG, Schierberl KC, Xiang JZ, Putorti ML, Berciano J, Poulin C, Brais B, Michaelides M, Weleber RG, Higgins JJ (2010) Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa. Am J Hum Genet 87:643–654

    Article  PubMed  CAS  Google Scholar 

  9. Keel SB, Doty RT, Yang Z, Quigley JG, Chen J, Knoblaugh S, Kingsley PD, De Domenico I, Vaughn MB, Kaplan J, Palis J, Abkowitz JL (2008) A heme export protein is required for red blood cell differentiation and iron homeostasis. Science 319:825–828

    Article  PubMed  CAS  Google Scholar 

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We thank the family members for their participation. We also thank Dr. S. Ogawa (Cancer Genome Project, The University of Tokyo) for his kind help to sequencing. This work was supported in part by KAKENHI (Grant-in-Aid for Scientific Research) on Scientific Research on Innovative Areas (Exploring Molecular Basis for Brain Diseases Based on Personal Genomics), Priority Areas (Applied Genomics), Integrated Database Project, and Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. H. I. is supported by a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists.

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Correspondence to Shoji Tsuji.

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Ishiura, H., Fukuda, Y., Mitsui, J. et al. Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1. Neurogenetics 12, 117–121 (2011).

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