Novel mosaic mutation in the dystrophin gene causing distal asymmetric muscle weakness of the upper limbs and dilated cardiomyopathy

Joana Ribeiro 1, Olinda Rebelo 1, Ana Fernández-Marmiesse 2 and Luís Negrão 1

1 Neuromuscular Disease Unit, Coimbra University and Hospital Centre, Coimbra, Portugal; 2 Unidad de Diagnóstico y Tratamiento de Enfermedades Metabólicas Congénitas (UDyTEMC), Hospital Clínico Universitario Santiago de Compostela

A group of heterogeneous muscle diseases are caused by dystrophin gene (DMD) mutations. We hereby present a male patient with a diagnosis of symptomatic dilated cardiomyopathy at 44 years-old who developed, soon after, weakness of distal right upper limb. At the age of 58, neurological examination revealed severe atrophy of right thenar muscles, flexion contractures on the right elbow, wrist and fingers, bilateral calf hypertrophy, myotatic areflexia in the upper limbs and hyporeflexia in the lower limbs. Manual muscle examination showed distal weakness of right upper limb muscles, severe on abductor pollicis brevis and extensor pollicis longus, and milder on interossei, finger extensors and brachioradialis muscles. Further testing revealed CK of 1500 U/L, a myopathic pattern on electromyography, and myopathic changes on right deltoid muscle biopsy, with immunohistochemistry showing focal sub-expression of dystrophin. Cardiac workup revealed a severe reduction in left ventricular ejection fraction, with a left ventricle of increased dimensions and global hypo-contractibility. A next-generation sequencing based panel for muscular diseases was performed and a nonsense mutation (c.C7525T) was identified in exon 51 of DMD gene, present in 70% of the gene readings (consistent with mosaicism).

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