Tag Archives: Michael Briggs Newcastle

RUBICON Network

Rubicon Members

  • Marco Ponzetti (UNIVAQ)
  • Alfredo Cappariello (UNIVAQ)
  • Suvro Chatterjee (UNIVANNA)
  • Karl Kadler (UMAN)
  • Michael Briggs (UNEW)
  • Bram van der Eerden (ERASMUS)
  • Michael Baldwin (Engedi)
  • Nadia Rucci (UNIVAQ)
  • Anna Teti (UNIVAQ)
  • Malcolm Collins (UCT)
  • Peter Magnusson (REGION H)

Absent from photo:-

  • John Bateman and Shireen Lamande (Melbourne)
  • Danny Chan (Hong Kong)
  • Checco Ramirez (New York)

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Genomics of Common and Rare Genetic Disease @MScGenomicsNcl

Study Day 2 of GNM8003 Genomics of Common and Rare Genetic Disease

Institute of Genetic Medicine, Newcastle University

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The exciting programme is as follows……programme

Recurrent COMP missense mutations

What are their prevalence and significance?

(No easy answer, but…………)EJHG 2014Having recently complied a comprehensive list of COMP mutations from 300 case studies published over the last 18 years (see here or download ejhg201430a) we set out to identify recurrent COMP mutations and determine their geographical/ethnic distribution.

Here are our “Top 6”  COMP mutations with the total number [n=] of reported cases :-

  • c.925G> p.(Gly309Arg) [n=4]
  • c.1153G>A p.(Asp385Asn) [n=13]
  • c.1318G>A p.(Gly440Arg) [n=7]
  • c.1552G>A p.(Asp518Asn) [n=4]
  • c.1569C>G p.(Asn523Lys) [n=4]
  • c.2152C>T p.(Arg718Trp) [n=8]

It is clear from this list that p.Asp385Asn is by far the most prevalent missense mutation and deserves further investigation.

Here are the details of all 13 individual cases reported in the literature:-

MED c.1153G>A p.(Asp385Asn) Kim et al AJMG 2011
MED c.1153G>A p.(Asp385Asn) Kim et al AJMG 2011
MED c.1153G>A p.(Asp385Asn) Kim et al AJMG 2011
MED c.1153G>A p.(Asp385Asn) Kim et al AJMG 2011
MED c.1153G>A p.(Asp385Asn) Song et al J Hum Genet 2003
MED c.1153G>A p.(Asp385Asn) Mabuchi et al Hum Genet 2003
MED c.1153G>A p.(Asp385Asn) Kennedy et al EJHG 2005
MED c.1153G>A p.(Asp385Asn) Kennedy et al EJHG 2005
MED c.1153G>A p.(Asp385Asn) Kennedy et al EJHG 2005
MED c.1153G>A p.(Asp385Asn) Kennedy et al EJHG 2005
MED non typical c.1153G>A p.(Asp385Asn) Jackson et al Hum Mut 2012
MED c.1153G>A p.(Asp385Asn) Jackson et al Hum Mut 2012
MED c.1153G>A p.(Asp385Asn) Jackson et al Hum Mut 2012

Points to note:-

  1. All individuals have the same nucleotide transition at c.1153G>A.
  2. The mutation appears equally in Asian (Kim, Song & Mabuchi)  and European (Kennedy & Jackson) studies suggesting increased prevalence is probably not due to a founder affect.
  3. Analysis of the Kennedy and Jackson studies confirms individuals are located throughout Europe [Switzerland n=1, The Netherlands n=2 and UK n=5] but it remains possible that there is a founder effect in the UK.
  4. Interestingly, a varient at the neighbouring reside (p.Asn386Asp) is one of the few confirmed and non-disease causing polymorphisms in COMP.