Genetic profile of Brazilian patients with dystrophinopathies.

Different types of mutations in the DMD gene underlie Duchenne muscular dystrophies (DMD) and Becker muscular dystrophies (BMD). Large deletions and duplications are the most frequent causative genetic alterations worldwide, but little is known about DMD/BMD genetic profile in Brazil. Hence, we recruited patients with DMD and BMD from 8 neuromuscular reference centers along the country, and performed a comprehensive molecular investigation that included Multiplex Ligation-dependent Probe Amplification and Next generation sequencing (NGS) analyses. We evaluated 199 patients from 177 unrelated families: 166 with DMD, 32 with BMD and 1 1.5 years old asymptomatic patient with persistent hiperCKemia. Overall, large deletions (58.2%) followed by nonsense mutations (12.4%) and large duplications (11.3%) were the most frequent variants in Brazilian families. Large deletions were less frequent in BMD than in DMD (44.8% vs 60.8%). We identified 19 new DMD variants. Nonsense mutations were significantly more frequent in patients from northeastern region than from southern/southeastern regions of Brazil (27.7% vs 8.5%, P < .05). Genetic profile of Brazilian patients with DMD/BMD is similar to previously reported cohorts, but it is not uniform across the country. This information is important to plan rational clinical care for patients in face of the new coming mutation-specific therapies.

[Distal myopathies: clinical, laboratory, electromyographic, histologic-histochemical analysis of 8 cases]. / Miopatias distais: análise clínica, laboratorial, eletromiográfica, histológico-histoquímica de oito casos.

Distal myopathies are uncommon diseases presenting difficulties in the classification by the lack of sufficient knowledge on pathogenesis. We describe eight cases of distal myopathies (five male and three female patients) whose symptoms started at the age of 10 in five and 20 in three. Symptoms started in the distal muscles of lower limbs, following decreased strength in the distal portion of upper limbs, and later on involvement of proximal muscles. Serum enzymes increase was slight in five, moderate in one, and important in two. EMG suggested primary myopathy in four, denervation in two, and was mixed type in another. Muscle biopsies showed features of myopathy and denervation in two cases, active chronic myopathy in five, and chronic myopathy in another. Four cases had vacuoles with positive acid phosphatase reaction and in two cases rimmed vacuoles were found. Six cases had increase of focal phosphatase acid in the muscle fibers suggesting a lissome participation in the pathogenesis of the disease. Two cases were classified as recessive autosomal distal myopathy (Welander variant), two recessive autosomal (Miyoshi type), two autosomal recessive with rimmed vacuole (Myzuzawa and Nonaka type), and two as miscellany type.