Phenotypic Characterization of a Family With An In-frame Deletion in the DMD Gene and Variable Penetrance.
Duchenne muscular dystrophy is a disorder with variable expression caused by framedisrupting mutations in the dystrophin gene. It is characterized by progressive muscle weakness and dilated cardiomyopathy. In-frame dystrophin mutations cause a clinically moderate disorder named Becker muscular dystrophy. Our aim was to study the clinical and genetic characteristics of a family with inherited cardiomyopathy and Becker muscular dystrophy. The index case was diagnosed with psychomotor retardation at 5 years of age. Asymmetric left ventricular hypertrophy and a long QT interval were evidenced at the age of 12. Mild muscular weakness was developed subsequently. Three genetic variants were identified in the index case: p.Arg891Alafs*160 in the MYBPC3 gene, p.Thr263Met in the KCNJ5 gene, and p.Ser2437_Ile2554delinsPhe in the DMD gene. The latter was expected to generate an in-frame deletion of exons 51 and 52 of the dystrophin gene. A family study revealed that the father and 3 uncles were carriers of the MYBPC3 mutation. The mother and a maternal grandfather were carriers of the other 2 variants. The 80-year-old grandfather, who had the dystrophin mutation, showed no sign of cardiomyopathy or muscular weakness. The deletion of exons 51 and 52 in the DMD gene, which has been proposed as one of the therapeutic strategies for Duchenne, is consistent with a normal life expectancy and the absence of myopathic symptoms in hemizygous males.
['Perez-Sanchez|Inmaculada|I|', 'Sabater-Molina|Maria|M|', 'Rocamora|Maria Elisa Nicolas|MEN|', 'Glover|Guillermo|G|', 'Escudero|Fuensanta|F|', 'de Mingo Casado|Pedro|P|', 'Gimeno-Blanes|Juan Ramon|JR|']
D000369:Aged, 80 and over D002352:Carrier Proteins D002675:Child, Preschool D016189:Dystrophin D005260:Female D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels D006801:Humans D008297:Male D020388:Muscular Dystrophy, Duchenne D009154:Mutation D019683:Penetrance D010641:Phenotype D011379:Prognosis D017384:Sequence Deletion
Deletion Duchenne muscular dystrophy Dystrophin Cardiomyopathy MYBPC3 Myopathic symptoms exons.