Genetic analysis of novel hereditary neuropathy mapping to chromosome 1

• Project/Area Number: 26460411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kurume University
• Principal Investigator: SHIROH MIURA 久留米大学, 医学部, 講師 (00441650)
• Co-Investigator(Kenkyū-buntansha): 柴田 弘紀 九州大学, 生体防御医学研究所, 准教授 (80315093)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IQGAP3 / 遺伝性ニューロパチー / エクソーム / 連鎖解析 / non coding RNA

Outline of Final Research Achievements

To identify the causative variation for a clinically and genetically new type of autosomal dominant motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough, we studied a Japanese pedigree with the disease consisted with 19 family members including 9 patients in 5 generations. On multipoint linkage analysis of the pedigree, maximum LOD scores of > 2.0 was obtained on 1p13.3-q23 (LOD = 2.24). The exome sequencing upon seven patients and one healthy relative from the pedigree revealed one causative single nucleotide variant (SNV) located in IQGAP3 which is associated with neurite outgrowth. The SNV is highly conserved among vertebrates. Real time quantitative PCR analysis of peripheral blood samples showed the mRNA expression level of IQGAP3 was significantly higher in a patient. The SNV alters the splicing of IQGAP3 and also located within a non-coding RNA which may affect the expression of IQGAP3.

Research Products

• [Journal Article] A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia (2016)
  • Author(s): Miura S, Morikawa T, Fujioka R, Kosaka K, Yamada K, Hattori G, Motomura M, Taniwaki T, Shibata H.
  • Journal Title: Eur J Med Genet Volume: 59 Issue: 8 Pages: 413-416
  • DOI: 10.1016/j.ejmg.2016.05.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Essential Tremor with Aspartic Acidemia (2016)
  • Author(s): Miura S, Fujioka R, Taniwaki T.
  • Journal Title: The Kurume Medical Journal Volume: 63 Issue: 3.4 Pages: 81-84
  • DOI: 10.2739/kurumemedj.MS00015
  • NAID: 130005661600
  • ISSN: 0023-5679, 1881-2090
  • Peer Reviewed
• [Journal Article] 片側体幹感覚障害を認めた中心後回梗塞 (2016)
  • Author(s): 三浦史郎、内山雄介、佐野謙、植田晋一郎、谷脇考恭
  • Journal Title: 神経内科 Volume: 84 Pages: 105-107
  • Peer Reviewed
• [Journal Article] Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus. (2015)
  • Author(s): Hauser MA, Aboobakar IF, Liu Y, Miura S, Whigham BT, Challa P, Wheeler J, Williams A, Santiago-Turla C, Qin X, Rautenbach RM, Ziskind A, Ramsay M, Uebe S, Song L, Safi A, Vithana EN, et al
  • Journal Title: Hum Mol Genet Volume: 24 Issue: 22 Pages: 6552-6563
  • DOI: 10.1093/hmg/ddv347
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A novel missense mutation of RYR1 in familial idiopathic hyper CK-emia. (2015)
  • Author(s): K. Sano, S. Miura, T. Fujiwara, R. Fujioka, A. Yorita, K. Noda, H. Kida, K. Azuma, S. Kaieda, K. Yamamoto, T. Taniwaki, Y. Fukumaki, and H. Shibata
  • Journal Title: Journal of the Neurological Sciences Volume: 356 Issue: 1-2 Pages: 142-147
  • DOI: 10.1016/j.jns.2015.06.035
  • Peer Reviewed
• [Journal Article] First Japanese case of muscular dystrophy caused by a mutation in the anoctamin 5 gene (2015)
  • Author(s): Kida Hiroshi, Ken Sano, Akiko Yorita, Shiro Miura, Mitsuyoshi Ayabe, Yukiko Hayashi, Ichizo Nishino, Takayuki Taniwaki
  • Journal Title: Neurology and Clinical Neuroscience Volume: 3 Issue: 4 Pages: 150-152
  • DOI: 10.1111/ncn3.175
  • Peer Reviewed
• [Presentation] Heterozygous missense mutation in SEC24A encoding a coat protein complex II vesicle associated with autosomal dominant spinocerebellar ataxia (2016)
  • Author(s): Morikawa T, Miura S, Kosaka K, Fujioka R, Sano K, Yorita A, Aoki K, Uchiyama Y, Taniwaki T, Shibata H.
  • Organizer: American Society of Human Genetics Annual Meeting 2016
  • Place of Presentation: Vancouver
  • Year and Date: 2016-10-21
  • Int'l Joint Research
• [Presentation] A missense mutation in the PPIG gene encoding the peptidyl-prolyl isomerase G in patients with autosomal dominant benign adult familial myoclonic epilepsy (2016)
  • Author(s): Fujioka R, Miura S, Yamada K, Morikawa T, Motooka H, Uchiyama Y, Aso Y, Kimura N, Sano K, Yamamoto K, Taniwaki T, Shibata H.
  • Organizer: American Society of Human Genetics Annual Meeting 2016
  • Place of Presentation: Vancouver
  • Year and Date: 2016-10-19
  • Int'l Joint Research
• [Presentation] Homozygous 4-bp deletion in the DDHD1 gene, resulting the complete deletion of DDHD domain, as a causative variant in a SPG28 patient (2016)
  • Author(s): Morikawa T, Miura S, Yamada K, Hattori G, Kosaka K, Fujioka R, Motomura M, Taniwaki T, Shibata H.
  • Organizer: International Congress of Human Genetics 2016
  • Place of Presentation: Kyoto
  • Year and Date: 2016-04-05
  • Int'l Joint Research
• [Presentation] Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough maps to chromosome 1p13.3-1q23. (2015)
  • Author(s): Miura S, Sano K, Kosaka K, Fujioka R, Saitsu H, Taniwaki T, Yamamoto K, Shibata H
  • Organizer: American Society of Human Genetics Annual Meeting 2015
  • Place of Presentation: Baltimore, MD, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] Genetic analysis for benign adult familial myoclonic epilepsy using linkage-assisted exome sequencing. (2014)
  • Author(s): Yamada K, Miura S, et al.
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-26
• [Presentation] A novel missense mutation of ryanodine receptor 1 (RYR1) in a Japanese idiopathic hyper CK-emia family. (2014)
  • Author(s): Sano K, Miura S, et al.
  • Organizer: American Society Human Genetics Annual Meeting 2014
  • Place of Presentation: San Diego
  • Year and Date: 2014-10-19