title: [Physical study of big fragments and search strategy of genes. Application to locus of infant spinal muscular atrophies].
abstract: Spinal muscular atrophies (SMA) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood SMAs are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a YAC contig of the 5q13 region spanning the disease locus was constructed that showed the presence of low copy-repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in 10 SMA patients. Moreover, deletions were strongly suggested in at least 18% of SMA type I patients by the observation of marked heterozygosity deficiency for the loci studied. These results indicate that deletion events are statistically associated with the severe form of SMA.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants-Malades, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Melki
authors.forename: S
authors.initials: S
authors.lastname: Lefebvre
authors.forename: L
authors.initials: L
authors.lastname: Burglen
authors.forename: P
authors.initials: P
authors.lastname: Burlet
authors.forename: O
authors.initials: O
authors.lastname: Clermont
authors.forename: P
authors.initials: P
authors.lastname: Millasseau
authors.forename: S
authors.initials: S
authors.lastname: Reboulet
authors.forename: B
authors.initials: B
authors.lastname: Benichou
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
authors.forename: D
authors.initials: D
authors.lastname: Le Paslier
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D002895:Chromosomes, Human, Pair 5; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D012091:Repetitive Sequences, Nucleic Acid; D014897:Spinal Muscular Atrophies of Childhood / Q000145:classification / Q000235:genetics*
vernacular_title: Etude physique des grands fragments et stratégies de recherche de gènes. Applications au locus des amyotrophies spinales infantiles.