Assessment of Nonallelic Genetic Heterogeneity of Chronic (Type II
and III) Spinal Muscular Atrophy
L.M. Brzustowicz, C. Merette, P.W. Kleyn,
T. Lehner , L.H. Castilla, G.K. Penchaszadeh , K. Das ,
T.L. Munsat, J. Ott , T.G. Gilliam
Human Heredity , 43(6), 380--387 (1993 Nov-Dec)
Abstract
We have previously reported the mapping of the chronic (type
II/intermediate and type III/mild/Kugelberg-Welander) form of the
childhood-onset spinal muscular atrophies (SMA) to chromosome
5q11.2-13.3, with evidence for nonallelic genetic heterogeneity
within a small sample of seven families [Brzustowicz et al., Nature
1990;344:540-541]. We now report the results of linkage analysis and
heterogeneity testing on a set of 38 families with chronic SMA.
Significant evidence for nonallelic heterogeneity was detected among
these families, with the predominant locus for chronic SMA mapping
to a 0.51-cM region on 5q, between the loci D5S6 and MAP1B. The
estimated proportion of linked families, alpha, was 0.91, with a
2.3-unit support interval of 0.75 to 0.98. The indication that some
families diagnosed with chronic SMA are not linked to chromosome 5q
must be considered in strategies to map the SMA locus. The relevance
of these findings to acute SMA (SMA type I, severe, Werdnig-Hoffmann
disease) is still unknown.
