title: ATAXIN2 CAG-repeat length in Italian patients with amyotrophic lateral sclerosis: risk factor or variant phenotype? Implication for genetic testing and counseling.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurons. Several studies indicated that intermediate CAG expansions in ataxin-2 gene (ATXN2) are associated with increased risk of ALS. We analyzed ATXN2 CAG repeats in 658 sporadic ALS patients (SALS), 143 familial ALS cases (FALS), 231 sporadic ataxic subjects, and 551 control subjects. The frequency of ATXN2 alleles with 27-30 repeats was similar in SALS and control subjects. Fifteen SALS subjects carried ≥ 31 CAG repeats. This difference was statistically significant (p = 0.0014). No alleles with ≥ 34 CAG were found. In FALS, the distribution of ATXN2 alleles was similar to control subjects. Our results further contributed in refining CAG-repeat range significantly associated with sporadic ALS. Literature data and our findings indicate that only alleles with ≥ 31 CAG may represent low-penetrance disease/susceptibility alleles associated with variable neurodegenerative phenotypes, including cerebellar ataxia, parkinsonism, and ALS. Overlapping phenotypes should be considered in genetic testing and counseling, both for patients and at-risk family members.
authors.affiliation: Genetics of Neurodegenerative and Metabolic Disorders, Fondazione-IRCCS, Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
authors.forename: Viviana
authors.initials: V
authors.lastname: Pensato
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Nanetti
authors.forename: Alessia
authors.initials: A
authors.lastname: Castucci
authors.forename: Barbara
authors.initials: B
authors.lastname: Castellotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D000067528:Ataxins; D002681:China / Q000453:epidemiology; D005260:Female; D005817:Genetic Counseling; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors
chemical_list: D000067528:Ataxins; D005819:Genetic Markers; D009419:Nerve Tissue Proteins