Spinal muscular atrophy is not the result of mutations at the beta-hexosaminidase or GM2-activator locus.
The disease locus for the clinically heterogeneous childhood spinal muscular atrophies (SMA) maps to the chromosome 5 subregion, 5q11.2-13.3. The beta-subunit of beta-D-N-acetylhexosaminidase (hexosaminidase) (EC 3.2.1.52) (Hex B) maps to the same region, and the protein required for substrate recognition by this enzyme, GM2-activator protein, likewise maps to chromosome 5. We have investigated the possibility of allelic variation among some forms of SMA and hexosaminidase deficiency. Recombination between the Hex B and SMA loci eliminates this enzyme as a candidate site for defects causing the illness. Furthermore, we show that, despite previous evidence to the contrary, the GM2-activator locus does not map to chromosome 5, thereby eliminating it as a candidate gene for SMA.
Kleyn
P W
PW
Department of Psychiatry, Columbia University, New York, NY 10032.
Brzustowicz
L M
LM
Wilhelmsen
K C
KC
Freimer
N B
NB
Miller
J M
JM
Munsat
T L
TL
Gilliam
T C
TC
D000595:Amino Acid Sequence; D004247:DNA / Q000032:analysis; D004586:Electrophoresis; D049289:G(M2) Activator Protein; D005784:Gene Amplification; D005796:Genes; D054819:Hexosaminidase B; D006801:Humans; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
D049289:G(M2) Activator Protein; D011506:Proteins; D004247:DNA; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases