Variable Cardiac Involvement in Tunisian Siblings Harboring FKRP Gene Mutations

Abstract

Mutations in the gene encoding fukutin-related protein (FKRP) cause limb-girdle muscular dystrophy 2I (LGMD2I) and congenital muscular dystrophy (MDC1C). Cardiac involvement was frequently reported with numerous mutations including C826A and 1364C > A mutations. The original Tunisian family with LGMD2I included 12 patients sharing the LGMD phenotype and homozygous to the 1486T > A mutation but who did not display any cardiac involvement. In this study, we report the clinical data, cardiac assessment and mutation analysis in four sibs belonging to a second Tunisian LGMD2I family. All patients showed the LGMD phenotype, the oldest brother and sister had mild cardiac involvement, whereas two twin sisters displayed severe cardiomyopathy leading to death. The patients shared the compound heterozygous 1486T > A, 1364C > A mutation in the FKRP gene suggesting that the association of a compound heterozygous state of mutation responsible for LGMD2I and the MDC1C phenotype could lead to cardiac involvement.

Key words

fukutin-related protein gene (FKRP) - LGMD2I - MDC1C - cardiac involvement

References

• 1 Brockington M, Yuva Y, Prandini P. et al . Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.  Hum Mol Genet. 2001;  10 2851-2859
• 2 Driss A, Noguchi S, Amouri R. et al . Fukutin-related protein gene mutated in the original kindred limb-girdle MD 2I.  Neurology. 2003;  60 1341-1344
• 3 Louhichi N, Triki C, Quijano-Roy S. et al . New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities. Identification of a founder mutation in Tunisian families.  Neurogenetics. 2004;  5 27-34
• 4 Mercuri E, Brockington M, Straub V. et al . Phenotypic spectrum associated with mutations in the fukutin-related protein gene.  Ann Neurol. 2003;  53 537-542
• 5 Muller T, Krasnianski M, Witthaut R, Deschauer M, Zierz S. Dilated cardiomyopathy may be an early sign of the C826A fukutin-related protein mutation.  Neuromuscul Disord. 2005;  15 372-376
• 6 Poppe M, Bourke J, Eagle M. et al . Cardiac and respiratory failure in limb-girdle muscular dystrophy 2I.  Ann Neurol. 2004;  56 738-741
• 7 Poppe M, Cree L, Bourke J. et al . The phenotype of limb-girdle muscular dystrophy type 2I.  Neurology. 2003;  60 1246-1251
• 8 Quijano-Roy S, Marti-Carrera I, Makri S. et al . Brain MRI abnormalities in muscular dystrophy due to FKRP mutations.  Brain Dev. 2006;  28 232-242
• 9 Vignos PJ, Archibald KC. Maintenance of ambulation in childhood muscular dystophy.  J Chron Dis. 1960;  12 273
• 10 Walter MC, Petersen JA, Stucka R. et al . FKRP (826C > A) frequently causes limb-girdle muscular dystrophy in German patients.  J Med Genet. 2004;  41 e50

Correspondence