Insights into genotype-phenotype correlations in spinal muscular atrophy: A retrospective study of 103 patients

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 cl...

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Bibliographic Details
Published in:Muscle & nerve 2011-01, Vol.43 (1), p.26-30
Main Authors: Petit, Florence, Cuisset, Jean-Marie, Rouaix-Emery, Nathalie, Cancés, Claude, Sablonnière, Bernard, Bieth, Eric, Moerman, Alexandre, Sukno, Sylvie, Hardy, Noah, Holder-Espinasse, Muriel, Manouvrier-Hanu, Sylvie, Vallée, Louis
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain Stem - pathology
Brain Stem - physiopathology
brainstem involvement
Child
Child, Preschool
Cohort Studies
Diseases of striated muscles. Neuromuscular diseases
Electrodiagnosis. Electric activity recording
Female
Genetic Predisposition to Disease - genetics
Genotype
Genotype & phenotype
genotype-phenotype correlations
Humans
Infant
Infant, Newborn
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
Muscular Atrophy, Spinal - genetics
Muscular Atrophy, Spinal - pathology
Muscular Atrophy, Spinal - physiopathology
Nervous system
Neurology
Phenotype
Retrospective Studies
SMN1
SMN2
spinal muscular atrophy
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Summary: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. Muscle Nerve, 2011
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.21832