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.

RGA Medical Event: “Newcastle Achondroplasia Symposium”

RGA LogoRGA Medical Event: Newcastle Achondroplasia Symposium

A great initiative being organised Dr. Michael Wright and Dr. Melita Irving.

The first Newcastle Achondroplasia Symposium on 20th and 21st September 2014


This event is being hosted jointly by Newcastle upon Tyne Hospitals, Newcastle University, the Evelina Children’s Hospital and the Restricted Growth Association (RGA) and has been sponsored by the British Medical Association and the Skeletal Dysplasia Group.

SDG logo

This an exciting opportunity to meet and discuss healthcare provision with doctors and other healthcare professionals from hospitals with a particular interest in providing services for people with achondroplasia.

The aim is to develop guidelines to help improve the health services that are available for all people with achondroplasia.

The symposium will be held at the Institute of Genetic Medicine, Centre for Life, Newcastle upon Tyne.

See here for more information on Restricted Growth Association.