Genetics of familial amyotrophic lateral sclerosis
نویسنده
چکیده
Amyotrophic lateral sclerosis (ALS) is an adultonset, rapidly progressive neurodegenerative disorder, caused by the selective loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Neuronal degeneration leads to weakness, muscular atrophy, and spasticity that evolve to paralysis. The typical age at onset is between 50 and 60 years, and the global incidence is 1-2 new cases per 100.000 individuals every year. The disease is fatal within 2-5 years of onset, generally due to respiratory failure. As the cause of ALS is still unknown, there is presently no effective treatment for it (Rowland et al., 2001). Although the majority of ALS cases are sporadic (sporadic ALS, SALS), 10% of patients have a positive familial anamnesis for motor neuron disease, generally with an autosomal-dominant inheritance pattern, although recessive pedigrees have been described (familial ALS, FALS) (Mulder et al., 1986). The clinical phenotype of FALS cases is usually indistinguishable from SALS. However, in comparison to SALS, FALS is characterized by an equal male:female sex ratio, an earlier age at onset, and, generally a longer disease duration. The first signs of the disease often occur in the lumbosacral segment, and atypical symptoms may be present at onset (Li et al., 1988; Strong et al., 1991; de Belleroche et al., 1995; Majoor-Krakauer et al., 2003). To date, 12 disease loci have been reported to be associated with typical ALS or atypical motor neuron diseases and two loci with ALS with frontotemporal dementia (ALS-FTD) (Table I). The first major breakthrough in our understanding of the genetic basis of FALS came in 1993 with the discovery of pathogenic mutations in the superoxide dismutase 1 (SOD1) gene (Rosen et al., 1993). SOD1 mutations are the most frequently identified cause of FALS, accounting for ~20% of all patients. An exciting step forward in ALS genetics is represented Genetics of familial amyotrophic lateral sclerosis
منابع مشابه
An Iranian familial amyotrophic lateral sclerosis pedigree with p.Val48Phe causing mutation in SOD1: a genetic and clinical report
Objective(s): Amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disorder, is the most common motor neuron disease in European populations. Approximately 10% of ALS cases are familial (FALS) and the other patients are considered as sporadic ALS (SALS). Among many ALS causing genes that have been identified, mutations in SOD1 and C9orf72 are the most common genetic causes...
متن کاملFamilial amyotrophic lateral sclerosis, a historical perspective
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease of the upper and lower motor neuron of unknown etiology. Although a familial cause for this disease has been suspected early one, it is only in the past two decades that advances in modern genetics led to the identification of more than 10 genes linked to familial ALS and helped us understand some of the complex genetic and envi...
متن کاملThe genetics of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a devastating disorder of still unknown aetiology and pathogenesis. It is characterized by a progressive and selective loss of motor neurons in the brain and spinal cord. The majority of ALS cases (90%) are sporadic and in approximately 10% the disorder is familial. In the light of recent studies, the familial forms might however be more frequent. The arti...
متن کاملGenetics of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) was first described by Charcot in 1869 as what we would now call a sporadic disease-a disease believed to occur without a strong genetic influence. Only within the past 10 years has it been possible to fully explore genetic influence on disorders that seem to occur sporadically but likely result from the convergence of multiple genetic and environmental facto...
متن کاملA novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13.
M otor neurone disease includes a heterogeneous group of disorders with motor neurone involvement, such as amyotrophic lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, and primary lateral sclerosis. Amyotrophic lateral sclerosis is the most common adult onset form of motor neurone disease and involves the lower and upper motor neurones. It is characterised by progressi...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2011