RESUMO
We report a family with an X-linked recessive muscular dystrophy characterised by exercise-induced myalgia, recurrent pigmenturia and mild proximal muscle involvement. Immunocytochemical and immunoblotting analysis in muscle, using the antibody directed against the rod domain of dystrophin, revealed a loss of immunoreactivity, but the immunolabelling using the antibodies directed against the COOH and NH2 domains of dystrophin were almost normal. The immunoreactions for alpha-sarcoglycan, gamma-sarcoglycan and beta-dystroglycan were normal. In the five male patients of this family with increased serum creatine kinase levels (from x8 to x50), mass spectrometry screening of the urine revealed a large increase in glycerol elimination which was quantified by enzymatic assay (from x14 to x39). An in-frame deletion of the dystrophin gene (exons 13-29) was found in the same five males and in three carrier females. All the deleted chromosomes also carried a missense mutation at nucleotide 947 of the Xp glycerol kinase (GK) gene resulting in a Thr to Met substitution at codon 278. These findings indicate that the two mutations cosegregate on the same chromosome in this family. This is the first reported case of two physically independent mutations, within the DMD and GK genes, which are contiguous but several hundred kilobases apart.
Assuntos
Distrofina/genética , Ligação Genética , Glicerol Quinase/genética , Distrofias Musculares/genética , Mutação Puntual , Cromossomo X , Adolescente , Adulto , Criança , Pré-Escolar , Mapeamento Cromossômico , Feminino , Deleção de Genes , Humanos , Masculino , Linhagem , SíndromeRESUMO
Anatomoclinical profile and follow-up of a glomerular nephropathy in a prepubertal girl with Charcot-Marie-Tooth disease is reported; striking common pattern features with the few cases previously published of such an association strongly suggest that renal involvement is possible in sensorineural neuropathies and may be one major factor in the overall prognosis of the disease.