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.
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U 393, Institut Necker-Enfants Malades, Paris, France. lviollet@afm.genethon.fr
Louis
L
Viollet
Annie
A
Barois
Jean G
JG
Rebeiz
Ziad
Z
Rifai
Philippe
P
Burlet
Mohammed
M
Zarhrate
Elodie
E
Vial
Michel
M
Dessainte
Brigitte
B
Estournet
Bernard
B
Kleinknecht
John
J
Pearn
Raymond D
RD
Adams
Jon A
JA
Urtizberea
Didier P
DP
Cros
Kate
K
Bushby
Arnold
A
Munnich
Suzie
S
Lefebvre
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