Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2‐13.3 (SMA 5q)

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Abstract
We made phenotypic analysis of 14 families with spinal muscular atrophy (SMA) linking to chromosome 5q11.2-13.3 (SMA 5q), and 2 that may not map to this locus, to assess clinical symptoms among SMA families known to result from mutation at the identical gene/locus. Although the current number of families is still small, the correlation of clinical phenotype and molecular genotype supports 2 observations. First, SMA mutations at the 5q locus present with a broad continuum of clinical abnormalities, and 2nd, the single clearly unlinked family presents with an unusual phenotype characterized by relatively late onset and early death. Thus, there are as yet no unambiguous cases of typical SMA families that are clearly unlinked to the locus at 5q–ie, no clear cases of nonallelic heterogeneity. Analysis of SMA 5q families supports the view that, with certain exceptions, there is little phenotypic intrafamilial variability. When families were ranked by severity of disease there was a strong correlation with age of onset. Onset within the 1st few months was associated with early death, but not in all cases. With rare exception, onset after 1 year of age was associated with less severe disease and greater longevity.