Identification of the candidate gene for PFAPA syndrome

• Project/Area Number: 25860874
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Yokohama City University
• Principal Investigator: NAKASHIMA Mitsuko 横浜市立大学, 医学部, 助教 (20541965)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 全エクソーム解析 / 小児周期発熱 / バイオインフォマティクス

Outline of Final Research Achievements

We performed whole exome analysis for 45 samples of 12 families with PFAPA. Firstly, we searched the mutations in 6 known candidate genes(MEFV, MVK, TNFRS1A, LPIN2, NOD2, ELANE) for hereditary autoinflammatory syndromes, but we coud not detect any pathogenic mutations in these genes. Narrowing down the candidate variants in each family, we detected 26-98 candidate variants in the families with autosomal dominant inheritance model and 1-3 candidate variants in the sporadic families. We then searched the candidate genes whose variants were found in two or more families. However, we could not find any common genes having pathologcal mutations.

Research Products

• [Journal Article] Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3 (2014)
  • Author(s): Nakashima M, Kashii H, Murakami Y, Kato M, Tsurusaki Y, Miyake N, Kubota M, Kinoshita T, Saitsu H, Matsumoto N.
  • Journal Title: Neurogenet Volume: 15（3） Issue: 3 Pages: 193-200
  • DOI: 10.1007/s10048-014-0408-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Causative novel PNKP mutations and concomitant PCDH15 mutations in a patient with microcephaly with early-onset seizures and developmental delay syndrome and hearing loss (2014)
  • Author(s): Nakashima M, Takano K, Osaka H, Aida N, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N.
  • Journal Title: J Hum Genet Volume: 59（8） Issue: 8 Pages: 471-474
  • DOI: 10.1038/jhg.2014.51
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge-Weber syndrome. (2014)
  • Author(s): Nakashima M, Miyajima M, Sugano H, Iimura Y, Kato M, Tsurusaki Y, Miyake N, Saitus H, Arai H, Matsumoto N.
  • Journal Title: J Hum Genet. Volume: 59 Issue: 12 Pages: 691-3
  • DOI: 10.1038/jhg.2014.95
  • Peer Reviewed
• [Presentation] Sturge-Weber syndromeにおけるGNAQ体細胞変異の同定 (2014)
  • Author(s): 中島 光子,宮嶋 雅一、新井 一、加藤 光広、松本 直通
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: タワーホール船堀(東京都江戸川区)
  • Year and Date: 2014-11-22
• [Presentation] Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3 (2014)
  • Author(s): Mitsuko Nakashima, Hirofumi Kashii, Yoshiko Murakami, Mitsuhiro Kato, Yoshinori Tsurusaki, Noriko Miyake, Masaya Kubota, Taroh Kinoshita, Hirotomo Saitsu, Naomichi Matsumoto
  • Organizer: The American Society of Human Genetics, 2014 meeting
  • Place of Presentation: San Diego (CA, USA)
  • Year and Date: 2014-10-19 – 2014-10-21