Elevated Serum Creatine Kinase and Small Cerebellum Prompt Diagnosis of Congenital Muscular Dystrophy due to FKRP Mutations
1Molecular Medicine and Neuromuscular Unit, IRCCS Stella Maris, Pisa, Italy.Journal of child neurology (Impact Factor: 1.72). 02/2013; 29(3). DOI: 10.1177/0883073812474951
Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum.
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ABSTRACT: Congenital muscular dystrophies are a highly heterogeneous group of conditions. In the last few years the identification of several new genes encoding for both glycosyltransferases and structural proteins has expanded the spectrum of the known forms. New classifications based on combined clinical, genetic and pathological data include all the recently discovered genes and allow an easier identification of the different forms and insight on pathogenetic mechanisms. The aim of this review is to discuss the most recent advances in this field, providing a conceptual framework to help the understanding of the responsible mechanisms and, when available, an update on the therapeutic perspectives.Annals of Neurology 07/2012; 72(1):9-17. DOI:10.1002/ana.23548 · 9.98 Impact Factor
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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.Neuropediatrics 04/2008; 39(2):113-5. DOI:10.1055/s-2008-1081465 · 1.24 Impact Factor
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