title: Co-existence of frataxin and cardiac troponin T gene mutations in a child with Friedreich Ataxia and familial hypertrophic cardiomyopathy.
abstract: Friedreich Ataxia (FA) is a neurodegenerative disorder characterised by progressive gait disturbance, dysarthria, dysmetria and other coordination disorders. The genetic defect is represented by an expansion of GAA repeats in the frataxin gene (FRDA or X25). Hypertrophic cardiomyopathy is a common finding in FA, and it is widely recognised as specific for the diagnosis of disease status. In this study, we report the co-existence, in a 5-year old boy with FA, of a double mutation in two distinct genes [X25 (A allele: 850 triplets; B allele: 1000 triplets), and cardiac troponin T (TNNT2) (287G>A)]. TNNT2 gene mutations have been previously identified in individuals with a familial form of hypertrophic cardiomyopathy (FHC), an autosomal dominant inherited disease characterised by unexplained cardiac hypertrophy and high incidence of sudden death. Although we cannot rule out the impact of each gene defect on cardiac morphology, it is of interest that these two mechanisms may be acting in a synergistic fashion to produce the extreme degree of cardiac hypertrophy detected in the child. This is, to our knowledge, the first description of a double gene defect in individuals with FA and FHC.
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore," School of Medicine, Magna Graecia University, Catanzaro, Italy. cuda@unicz.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cuda
authors.forename: Andrea
authors.initials: A
authors.lastname: Mussari
authors.forename: Daniela
authors.initials: D
authors.lastname: Concolino
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Costanzo
authors.forename: Pietro
authors.initials: P
authors.lastname: Strisciuglio
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005621:Friedreich Ataxia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D033862:Iron-Binding Proteins; D008297:Male; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D020107:Troponin T / Q000235:genetics*; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D020107:Troponin T; D000096923:Frataxin