Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.
Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior horn cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the same chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.
Viollet
Louis
L
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U 393, Institut Necker-Enfants Malades, Paris, France. lviollet@afm.genethon.fr
Barois
Annie
A
Rebeiz
Jean G
JG
Rifai
Ziad
Z
Burlet
Philippe
P
Zarhrate
Mohammed
M
Vial
Elodie
E
Dessainte
Michel
M
Estournet
Brigitte
B
Kleinknecht
Bernard
B
Pearn
John
J
Adams
Raymond D
RD
Urtizberea
Jon A
JA
Cros
Didier P
DP
Bushby
Kate
K
Munnich
Arnold
A
Lefebvre
Suzie
S
D000328:Adult; D002648:Child; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002908:Chronic Disease; D017362:Cyclic AMP Response Element-Binding Protein; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins