Article

The objective of this work was to study the natural history of dystrophinopathies
and the genotype-phenotype correlations made possible by the development of the
clinical part of the French DMD database. The collection of 70,000 clinical data
for 600 patients with an average longitudinal follow-up of 12years enabled
clarification of the natural history of Duchenne and Becker muscular dystrophies
and clinical presentations in symptomatic females. We were able to specify the
phenotypic heterogeneity of motor, orthopedic and respiratory involvements
(severe, standard and intermediary form), of the cardiac disorder (severe,
standard or absent cardiomyopathy, absence of correlation between motor and
cardiac involvements), and of brain function (mental deficiency in the patients
with Becker muscular dystrophy, psychopathological disorders in
dystrophinopathies). Phenotypic variability did not correlate with a specific
mutational spectrum. We propose a model of phenotypic analysis based on the
presence or not of muscular and cardiac involvements (described by age at onset
and rate of progression) and brain involvement (described by the type and the
severity of the cognitive impairment and of the psychological disorders). The
methodology developed for the DMD gene can be generalized and used for other
databases dedicated to genetic diseases. Application of this model of phenotypic
analysis for each patient and further development of the database should
contribute substantially to clinical research providing useful tools for future
clinical trials.
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Langue : FRANCAIS