title: Insights into genotype-phenotype correlations in spinal muscular atrophy: a retrospective study of 103 patients.
abstract: Spinal muscular atrophy (SMA) is an autosomal recessive disorder associated with homozygous deletion of the survival motor neuron 1 gene (SMN1). Its centromeric copy gene, SMN2, is the major modifying factor. However, the genotype-phenotype correlation is incomplete and is therefore not useful in clinical practice. We studied a cohort of 103 patients in order to refine this correlation. In addition to standard disease severity data, we collected three additional criteria: age at death; brainstem involvement; and loss of ambulation. Gene dosage analysis was conducted by multiplex ligation-dependent probe amplification (MLPA). SMN2 copynumber was highly correlated with survival duration in SMA type I and ambulation conservation or loss in type III. Among SMA severity groups, it was not significantly different in cases with brainstem involvement. Although the SMN2 copynumber could provide prognostic indications, clinical discrepancies still exist among patients, suggesting the existence of unidentified modifying factors.
authors.affiliation: Service de Génétique Clinique, CHU Hôpital Jeanne de Flandre, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouaix-Emery
authors.forename: Claude
authors.initials: C
authors.lastname: Cancés
authors.forename: Bernard
authors.initials: B
authors.lastname: Sablonnière
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Alexandre
authors.initials: A
authors.lastname: Moerman
authors.forename: Sylvie
authors.initials: S
authors.lastname: Sukno
authors.forename: Noah
authors.initials: N
authors.lastname: Hardy
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.forename: Louis
authors.initials: L
authors.lastname: Vallée
mesh_terms: D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D012189:Retrospective Studies