title: [Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases].
abstract: 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.
authors: Laboratoire de génétique moléculaire, CHU de Montpellier, 640, avenue du Doyen-Gaston-Giraud, 34095 Montpellier cedex 5, France; Inserm U827, 640, avenue du Doyen-Gaston-Giraud, 34095 Montpellier cedex 5, France. Electronic address: vhumbertclaude@gmail.com.
authors: V
authors: V
authors: Humbertclaude
authors: D
authors: D
authors: Hamroun
authors: M-C
authors: MC
authors: Picot
authors: K
authors: K
authors: Bezzou
authors: C
authors: C
authors: Bérard
authors: O
authors: O
authors: Boespflug-Tanguy
authors: C
authors: C
authors: Bommelaer
authors: E
authors: E
authors: Campana-Salort
authors: C
authors: C
authors: Cances
authors: B
authors: B
authors: Chabrol
authors: M-C
authors: MC
authors: Commare
authors: J-M
authors: JM
authors: Cuisset
authors: C
authors: C
authors: de Lattre
authors: C
authors: C
authors: Desnuelle
authors: B
authors: B
authors: Echenne
authors: C
authors: C
authors: Halbert
authors: O
authors: O
authors: Jonquet
authors: A
authors: A
authors: Labarre-Vila
authors: M-A
authors: MA
authors: N'guyen-Morel
authors: M
authors: M
authors: Pages
authors: J-L
authors: JL
authors: Pepin
authors: T
authors: T
authors: Petitjean
authors: J
authors: J
authors: Pouget
authors: E
authors: E
authors: Ollagnon-Roman
authors: C
authors: C
authors: Richelme
authors: F
authors: F
authors: Rivier
authors: S
authors: S
authors: Sacconi
authors: V
authors: V
authors: Tiffreau
authors: C
authors: C
authors: Vuillerot
authors: C
authors: C
authors: Béroud
authors: S
authors: S
authors: Tuffery-Giraud
authors: M
authors: M
authors: Claustres
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D005821:Genetic Techniques; D006801:Humans; D008297:Male; D009043:Motor Activity; D020388:Muscular Dystrophy, Duchenne / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype
chemical_list: D016189:Dystrophin
keywords: Banque de données; Becker muscular dystrophy; Corrélations génotype-phénotype; Database; Duchenne muscular dystrophy; Dystrophie musculaire de Becker; Dystrophie musculaire de Duchenne; Phenotype; Phenotype-genotype correlations; Phénotype