title: Wide phenotypic spectrum of the TARDBP gene: homozygosity of A382T mutation in a patient presenting with amyotrophic lateral sclerosis, Parkinson's disease, and frontotemporal lobar degeneration, and in neurologically healthy subject.
abstract: Mutations in the TARDBP gene are described as a cause of autosomal dominant amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) with or without motor neuron involvement, and, recently, Parkinson's disease (PD). We hereby describe a family presenting the A382T mutation; two subjects were in the homozygous state, and two were in the heterozygous state. The index case, carrying the A382T mutation in the homozygous state, had an 8-year history of sporadic PD and 6 years later developed ALS and FTLD; his brother, carrying the same mutation in the homozygous state, and the other two family member carriers of the same mutation in the heterozygous state were without neurological signs and symptoms. This family confirms that mutation in transactive response (TAR)-DNA-binding protein 43 (TDP43), both the homozygous and the heterozygous state, may be found in subjects with different clinical conditions ranging from neurological disease to non-neurological disease. In addition, the aforementioned findings add to the debate for the ethical and psychological dilemmas about genetic counseling.
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Mosca
authors.forename: Christian
authors.initials: C
authors.lastname: Lunetta
authors.forename: Claudia
authors.initials: C
authors.lastname: Tarlarini
authors.forename: Francesca
authors.initials: F
authors.lastname: Avemaria
authors.forename: Eleonora
authors.initials: E
authors.lastname: Maestri
authors.forename: Mario
authors.initials: M
authors.lastname: Melazzini
authors.forename: Massimo
authors.initials: M
authors.lastname: Corbo
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000151:congenital / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000151:congenital / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins