title: The speech and language FOXP2 gene modulates the phenotype of frontotemporal lobar degeneration.
abstract: The FOXP2 gene is mutated in a severe monogenic form of speech and language deficits, but no study on the influence of genetic variations within FOXP2 in neurological disorders characterized by language impairment is available yet. In the present study, we investigated the impact of common FOXP2 polymorphisms with regard to frontotemporal lobar degeneration (FTLD). Two-hundred ten FTLD patients underwent clinical and a wide standardized neuropsychological examination as well as brain imaging. In all patients, and in 200 age-matched healthy controls, four FOXP2 polymorphisms were evaluated, namely rs2396753, rs1456031, rs17137124 and rs1852469. SPECT images were analyzed by Statistical Parametric Mapping (SPM5). No significant differences of the four FOXP2 polymorphisms in genotype distribution and allele frequency between FTLD and controls were observed. A significant and specific association between rs1456031 TT and rs17137124 TT genotypes and verbal fluency scores was reported. The two polymorphisms showed an addictive effect. When the analysis was computed on the number of observations over time, and 391 assessments considered, comparable results were obtained. FTLD patients carrying at-risk polymorphisms showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus, and putamen, compared to the non-carriers (p < 0.005). Genetic variations within FOXP2 do not represent a genetic risk to FTLD per se, but modulate FTLD presentation when disease is overt, affecting language performances and leading to hypoperfusion in language-associated brain areas.
authors.affiliation: Centre for Brain Aging and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Maura
authors.initials: M
authors.lastname: Cosseddu
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Alice
authors.initials: A
authors.lastname: Papetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Agosti
authors.forename: Barbara
authors.initials: B
authors.lastname: Bigni
authors.forename: Carlo
authors.initials: C
authors.lastname: Cerini
authors.forename: Barbara
authors.initials: B
authors.lastname: Paghera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bellelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
mesh_terms: D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D057174:Frontotemporal Lobar Degeneration / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D007802:Language; D007806:Language Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013060:Speech / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors