title: De novo and inherited deletions of the 5q13 region in spinal muscular atrophies.
abstract: Spinal muscular atrophies (SMAs) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood spinal muscular atrophies are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a yeast artificial chromosome 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 nine unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18 percent 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 spinal muscular atrophy.
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: Reboullet
authors.forename: B
authors.initials: B
authors.lastname: Bénichou
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
authors.forename: D
authors.initials: D
authors.lastname: Le Paslier
mesh_terms: D000483:Alleles; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast; D002895:Chromosomes, Human, Pair 5; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*
chemical_list: D005819:Genetic Markers