Abstract
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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Acknowledgments
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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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). https://doi.org/10.1007/s10048-010-0271-4
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DOI: https://doi.org/10.1007/s10048-010-0271-4