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.

[1]  T. Gilliam,et al.  Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2‐13.3 (SMA 5q) , 1990, Neurology.

[2]  M. Lathrop,et al.  Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14 , 1990, The Lancet.

[3]  T. Lehner,et al.  Genetic homogeneity between acute and chronic forms of spinal muscular atrophy , 1990, Nature.

[4]  M. Lathrop,et al.  Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q , 1990, Nature.

[5]  M. Leppert,et al.  Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q1 1.2–13.3 , 1990, Nature.

[6]  N. Freimer,et al.  Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia. , 1989, Genomics.

[7]  A. Kahn,et al.  Msp1 RFLP in the human hexosaminidase beta peptide (Hex B) gene. , 1989, Nucleic acids research.

[8]  R. Navon,et al.  Hexosaminidase a deficiency manifesting as spinal muscular atrophy of late onset , 1988, Annals of neurology.

[9]  S. Schuster,et al.  Characterization of the human HEXB gene encoding lysosomal beta-hexosaminidase. , 1988, Genomics.

[10]  H. Willard,et al.  PstI RFLP in the human hexosaminidase (HEXB) gene on chromosome 5. , 1987, Nucleic acids research.

[11]  M. Fox,et al.  An anonymous human single copy genomic clone, D5S6 (M4) on chromosome 5 identifies a three allele RFLP. , 1986, Nucleic acids research.

[12]  H. Mitsumoto,et al.  Motor neuron disease and adult hexosaminidase a deficiency in two families: Evidence for multisystem degeneration , 1985, Annals of neurology.

[13]  K. Sandhoff,et al.  Mapping of the gene coding for the human GM2 activator protein to chromosome 5 , 1985, Annals of human genetics.

[14]  R. Navon,et al.  Clinical and genetic variations in the syndrome of adult GM2 gangliodosis resulting from hexosaminidase a deficiency , 1984, Annals of neurology.

[15]  A. Feinberg,et al.  "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. , 1984, Analytical biochemistry.

[16]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[17]  T. Gilliam,et al.  Cystic fibrosis is not caused by a defect in the gene coding for human complement C3. , 1983, Molecular biology & medicine.

[18]  J. Wasmuth,et al.  Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5 , 1982, Molecular and cellular biology.

[19]  L. Rowland,et al.  Juvenile spinal muscular atrophy: A new hexosaminidase deficiency phenotype , 1981, Annals of neurology.