MUTATION IN BRIEF HUMAN MUTATION Mutation in Brief #490 (2002) Online © 2002 WILEY-LISS, INC. DOI: 10.1002/humu.9019 Received 10 October 2001; accepted revised manuscript 28 December 2001. Co-existence of Frataxin and Cardiac Troponin T Gene Mutations in a Child with Friedreich Ataxia and Familial Hypertrophic Cardiomyopathy Giovanni Cuda 1 *, Andrea Mussari 2 , Daniela Concolino 2 , Francesco S. Costanzo 1 , and Pietro Strisciuglio 2 1 Department of Experimental and Clinical Medicine “G. Salvatore,” and 2 Department of Pediatrics, School of Medicine, Magna Græcia University, Catanzaro, Italy. *Correspondence to: Giovanni Cuda, Department of Experimental and Clinical Medicine, School of Medicine, Magna Græcia University, Catanzaro, Via T. Campanella, 115, I-88100 Catanzaro, Italy; Tel.: +39 961 712386; Fax: +39 961 770296; E-mail: cuda@unicz.it Contract grant sponsors: COFIN 1999 (MURST), CLUSTER C-04 (MURST), TELETHON, POP Regione Calabria (1994/99) Communicated by Mark H. Paalman 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. © 2002 Wiley-Liss, Inc. KEY WORDS: Friedreich Ataxia; FA; FRDA; hypertrophic cardiomyopathy, familial; FHC; X25, TNNT INTRODUCTION Friedreich ataxia (FA) is one of the most common forms of autosomal recessive ataxia (Ackroyd et al., 1984). This disorder, involving the spinocerebellar tracts, dorsal columns, pyramidal tracts and, to a lesser extent, the cerebellum and medulla, is mainly characterised by progressive gait disturbance, dysarthria, dysmetria and other coordination disorders. The triad of hypoactive knee and ankle jerks and preadolescent onset is commonly regarded as sufficient for diagnosis. Cardiac involvement is conspicuous in some cases and it is mainly represented by a variable degree of hypertrophy. Nearly one half of FA patients usually die of heart failure (Hewer, 1968). The