[Detection of carriers and diagnosis of Duchenne's muscular dystrophy by DNA analysis]. / Detección de portadoras y diagnóstico de la distrofia muscular de Duchenne mediante análisis del ADN.

Carrier detection and prenatal diagnosis of Duchenne muscular dystrophy can be, now, more accurately performed with the DNA recombinant techniques. The segregation pattern of DMD gen can be studied using the genetic variants detected at the DNA level (RFLPs) as markers. Cloned fragments within or very close to the gene (intragenic or extragenic probes) are used to reveal the RFLPs. Three families at risk for DMD were studied. Hybridization with extra or intragenic probes was performed and the analyses of several markers allows us to identify the X chromosome carrying the DMD gene. Carrier diagnosis was possible in all three families and a prenatal diagnosis in a carrier mother showed a risk probability of male affected fetus of 93-95%.

[2 families with benign myopathy predominantly on the limb girdle with dominant autosomal heredity]. / Deux familles de myopathies bénignes prédominant sur les ceintures d'hérédité autosomique dominante.

Very few authenticated cases of benign muscular dystrophy affecting mainly the girdles and of dominant autosomal inheritance have been documented. Two families were seen with this type of transmission, and certain common characteristics noted: proximal weakness and amyotrophy, frequency of muscle contractures, mainly distal, true calf hypertrophy, slow progression and benign nature and finally a fairly uniform semiology in the same family, an atypical finding in dominant autosomal hereditary disease.

Possible manifestation of the dystrophic X chromosome in muscle cultures from carriers of Duchenne muscular dystrophy.

Multilayer cell clusters have been observed before confluence and before myotube formation in muscle cell cultures derived from open biopsies of 7 of 14 (50%) female carriers of Duchenne muscular dystrophy, and in a high percentage of other dystrophic cultures. By contrast, this abnormality was seen in only 12 of 204 (6%) muscle biopsies from patients with other neuromuscular disorders. It appears that cluster formation is independent of the amount of connective tissue present in vivo, because histopathological analysis of the carrier biopsies showed increased endomysial connective tissue in only two cases. These results suggest that cluster formation is an expression of a myogenic defect and that it may be a manifestation of the genetic abnormality in X-linked muscular dystrophy.

Significance of serum myoglobin in neuromuscular diseases and in carrier detection of Duchenne muscular dystrophy.

In a retrospective study, the serum myoglobin concentration (S-myoglobin) was determined in patients with neuromuscular diseases and in carriers of Duchenne muscular dystrophy (DMD). Myoglobin was quantified by a sensitive radioimmunoassay. Serum creatine kinase (CK, EC 2.7.3.2) activity (S-CK) and serum creatine kinase B-subunit activity (S-CKB) were determined for comparison. Sera from 70 patients with various neuromuscular diseases and from 17 female relatives of patients with DMD were analysed. Increased levels of S-myoglobin were found both in dystrophic and in spinal myopathies. Because of a marked overlap of the range of values between the different dystrophic myopathies and even between the dystrophic and the spinal myopathies, S-myoglobin is of little value in the final diagnosis of neuromuscular diseases. In the detection of carriers of DMD, simultaneous determination of S-myoglobin and S-CK gave a higher detection rate compared to the detection rate with S-CK. S-CKB was normal in all carriers and only elevated in some of the patients with DMD and limb girdle muscular dystrophy.