• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular basis of congenital central hypoventilation syndrome : PHOX2B mutation and its haplotypes

Research Project

Project/Area Number 21591411
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionYamagata University

Principal Investigator

SASAKI Ayako  山形大学, 医学部, 講師 (60333960)

Co-Investigator(Kenkyū-buntansha) HAYASAKA Kiyoshi  山形大学, 医学部, 教授 (20142961)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords先天性中枢性低換気症候群 / PHOX2B / アラニン伸長変異 / 不等姉妹染色分体交換 / ポリアラニン伸長変異
Research Abstract

With congenital central hypoventilation syndrome (CCHS), most patients carry de novo polyalanine expansion mutation in PHOX2B. We reported previously that de novo polyalanine expansion mutations were of paternal origin and derived from unequal sister chromatid exchange during spermatogenesis. In the present study, we analyzed the relation between the haplotypes and de novo polyalanine expansion in PHOX2B and confirmed the origin and expanded mechanism of de novo polyalanine expansion mutation. We also found that haplotypes carrying rs17884724 : A>C were detected frequently in seven-alanine expanded (27 alanine) mutant alleles, most prevalent mutations in CCHS. The allele with rs17884724 : A>C would make fewer nucleotide mismatches in the misalignment at crossing over than the allele without rs17884724 : A>C. High frequency ofrs17884724 : A>C in seven-alanine expansion mutations would also support the unequal crossover mechanism for polyalanine expansion.
More than 90% of the alanine expansion mutations had been considered to be de novo mutation, however, a recent report stated that 25% of patients inherited the alanine-expanded allele from their parents with somatic mosaicism or constitutive mutation. We studied inheritance in 45 unrelated families, and found that 10 patients (22%) inherited alanine expansion mutation from a parent with late-onset central hypoventilation syndrome or asymptomatic parents with somatic mosaicism. Genetic analysis is needed for definite diagnosis and effective genetic counseling.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (7 results)

All 2012 2011 2010

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (1 results)

  • [Journal Article] Slowly progressive sleep apnea in late-onset central hypoventilation syndrome2012

    • Author(s)
      Fujiwaki T, Hasegawa H, Arai H, Hayasaka K, Ohta S.
    • Journal Title

      Pediatr Int

      Volume: 254 Issue: 2 Pages: 290-292

    • DOI

      10.1111/j.1442-200x.2011.03431.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome2012

    • Author(s)
      Meguro T, Yoshida Y, Hayashi M, Toyota K, Otagiri T, Mochizuki N, Kishikawa Y, Sasaki A, Hayasaka K.
    • Journal Title

      J Hum Genet

      Volume: 22(in press) Issue: 5 Pages: 335-337

    • DOI

      10.1038/jhg.2012.27

    • NAID

      10030663222

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome2012

    • Author(s)
      Meguro T, Yoshida Y, Hayashi M, Toyota K, Otagiri T, Mochizuki N, Kishikawa Y, Sasaki A, Hayasaka K
    • Journal Title

      J.Hum Genet

      Volume: 22(In Press)

    • NAID

      10030663222

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 先天性中枢性低換気症候群におけるPHOX2B遺伝子異常について2011

    • Author(s)
      早坂清, 荒井博子, 吉田悠紀, 小田切徹州, 佐々木綾子
    • Journal Title

      日本小児科学会雑誌

      Volume: 115 Pages: 769-776

    • NAID

      10029385399

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome : rs17884724 : A>C is associated with seven-alanine expansion2010

    • Author(s)
      Arai H, Otagiri T, Sasaki A, Umetsu K, Hayasaka K.
    • Journal Title

      J. Hum. Genet

      Volume: 55 Pages: 4-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome : rs17884724:A>C is associated with 7-alanine expansion.2010

    • Author(s)
      Arai H, Otagiri T, Sasaki A, Umetsu K, Hayasaka K
    • Journal Title

      J Hum Genet 55

      Pages: 4-7

    • NAID

      10030733021

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 先天性中枢性低換気症候群におけるPHOX2B遺伝子異常について2011

    • Author(s)
      早坂清
    • Organizer
      第114回日本小児科学会総会
    • Place of Presentation
      東京都港区グランドプリンスホテル新高輪国際館パミール
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi