Genetic Susceptibility in the Irish Amyotrophic Lateral Sclerosis Population

Project Description

Funding Health Research Board/Various.
Principal Investigator Dr. Orla Hardiman & Professor Andrew Green.
Researchers Dr. Matthew Greenway, Dr. Bryan Traynor, Dr Sean Ennis and Dr Michael Alexander.
Duration 1997-present.
Collaborators
  1. Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland
  2. Department of Neurology, Beaumont Hospital, Dublin
  3. MassGeneral Institute for Neurodegenerative Diseases & Harvard Medical School, Boston, USA

Introduction

Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disease affecting young and middle-aged adults in Ireland, with an incidence of 2.6/100,000. It is characterised by progressive selective destruction of motor neurons.

The disease is familial in 10% of cases, exhibiting an autosomal dominant inheritance with incomplete penetrance. Mutations in the Cu/Zn superoxidase gene (SOD1) account for approximately 20% of patients with familial ALS.

There is evidence that genetically determined susceptibility factors may account for the development of ALS in the remaining 90% of individuals, with the non-familial form of the disease. However the precise nature of these susceptibility factors is presently unclear.

The Irish Motor Neurone Disease Research Group has managed a National Register of ALS since 1994, under the direction of Dr. Hardiman. All incident and prevalent cases of ALS are collected. The aim of this project is to study potential susceptibility factors in the Irish ALS population and to correlate clinical features with alterations in known and proposed susceptibility genes.

In addition, groups of novel candidate genes will be examined for any potential role in motor neuron degeneration.

Publications

  1. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis
    Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O.
    Epub. 2006 Feb 26.
  2. Association of the H63D polymorphism in the hemochromatosis gene with sporadic ALS
    Goodall EF, Greenway MJ, van Marion I, Carroll CB, Hardiman O, Morrison KE.
    Neurology. 2005 Sep 27;65(6):934-7.
  3. “True” Sporadic ALS Associated with a Novel SOD-1 Mutation
    M Alexander, B Traynor, N Miller, B Corr, E Frost, S McQuaid, F Brett, A Green, O Hardiman.
    Ann. Neurology Nov;52(5):680-3, 2002.
  4. A Novel Candidate Region for ALS on Chromosome 14q11.2.
    M Greenway, M Alexander, S Ennis, B Traynor, B Corr, E Frost, A Green, O Hardiman.
    Neurology Nov;63(10), 2004.