What is the true ££££ of a rare disease?

A very interesting study from Kate Bushby and colleagues

DMD study

While rare genetic diseases are by definition individually uncommon, they represent a enormous global health burden.

In the European Union alone an estimated 30 million people are affected by a rare disease with a prevalence of less than 1 in 2,000. Rare connective tissue diseases have an overall prevalence estimated at 1/2,000, while musculoskeletal disease in general have an overall prevalence of 1/130 newborns, reflecting their great diversity.

Many inherited connective tissue diseases are congenital, chronic, life threatening and associated with substantial morbidity, extensive and expensive heath care needs and considerable physiological stress and financial burden for affected families.

While the cost burden of rare connective tissue diseases in terms of illness and economic load is not known this recent study of Duchenne Muscular Dystrophy, with a prevalence of ~1 in 5,000, reported that the mean per-patient annual direct cost of illness was estimated at between 7 to 16 times higher than the mean per-capita health expenditure. Moreover, the indirect and informal costs, along with total societal and household burden, was even higher and increased substantially with disease progression.

Download the open access paper here.

Diagnosing skeletal dysplasia in India -a great success !

Progress in diagnosing skeletal dysplasia in a southern Indian hospital could serve as a model for other rare diseases and for developing countries

From OrphaNews September 2014

In India, genetic testing is available in cities but rarely in rural settings. In an article published in the American Journal of Medical Genetics, Nampoothiri et al. report the experience of skeletal dysplasia (SD) diagnosis in a hospital in Kerala, where half the population lives in rural areas. From November 2005 to April 2013, physicians were trained to conduct genetic counselling, evaluation and testing on families at risk of carrying some form of SD or related condition. With the remote assistance of specialists based abroad, for complex cases, and networks such as the European Skeletal Dysplasia Network, the hospital investigators diagnosed 514 cases of SD. Mutation analysis confirmed 109 cases, 54 cases were confirmed by enzyme analysis and the remaining 351 were diagnosed by clinical and radiological evaluation.

See the full article here or download as open access ajmga36668

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.