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Insights into genotype–phenotype correlations in spinal muscular atrophy: A retrospective study of 103 patients
Author(s) -
Petit Florence,
Cuisset JeanMarie,
RouaixEmery Nathalie,
Cancés Claude,
Sablonnière Bernard,
Bieth Eric,
Moerman Alexandre,
Sukno Sylvie,
Hardy Noah,
HolderEspinasse Muriel,
ManouvrierHanu Sylvie,
Vallée Louis
Publication year - 2011
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21832
Subject(s) - smn1 , multiplex ligation dependent probe amplification , spinal muscular atrophy , sma* , brainstem , medicine , atrophy , genotype , motor neuron , phenotype , gene dosage , age of onset , disease , pathology , oncology , biology , genetics , gene , gene expression , mathematics , combinatorics , exon
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