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Genetic epidemiology of amyotrophic lateral sclerosis
Author(s) -
MajoorKrakauer D,
Willems PJ,
Hofman A
Publication year - 2003
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1046/j.0009-9163.2002.00001.x
Subject(s) - amyotrophic lateral sclerosis , neurodegeneration , penetrance , genetics , dementia , family aggregation , c9orf72 , sod1 , medicine , gene , multifactorial inheritance , genetic predisposition , genetic epidemiology , frontotemporal dementia , neuroscience , biology , disease , pathology , phenotype , single nucleotide polymorphism , genotype
Amyotrophic lateral sclerosis (ALS) is a late onset, rapidly progressive and ultimately fatal neurological disorder, caused by the loss of motor neurons in the brain and spinal cord. Familial aggregation of ALS, with an age‐dependent but high penetrance, is a major risk factor for ALS. Familial ALS (FALS) is clinically and genetically heterogeneous. Three genes and linkage to four additional gene loci have been identified so far and may either predominantly lead to ALS (ALSI‐ALS6) or cause multisystem neurodegeneration with ALS as an occasional symptom (tauopathies, ALS‐dementia complex). This review presents a tentative classification of the “major” ALS genes and ALS “susceptibility” genes, that may act as susceptibility factors for neurodegeneration in interaction with other genetic or environmental risk factors. Considering that mutations in ALS genes explain approximately 10% of familial as well as sporadic ALS, and most remaining cases of the discase are thought to result form the interaction of several genes and environmental factors, ALS is a paradigm for multifactorial discases.