PMID- 3812484
OWN - NLM
STAT- MEDLINE
DCOM- 19870310
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 40
IP  - 1
DP  - 1987 Jan
TI  - Gaucher disease: genetic heterogeneity within and among the subtypes detected by 
      immunoblotting.
PG  - 15-31
AB  - The genetic heterogeneity of Gaucher disease subtypes and variants was 
      investigated by immunoblotting of fibroblast extracts. For these studies 
      polyclonal and monoclonal antibodies were raised to acid beta-glucosidase 
      preparations containing a single N-terminal amino acid sequence that was colinear 
      with that encoded by the beta-Glc cDNAs. Three forms (Mr approximately equal to 
      67,000, 64,000-61,000, and 58,000) of cross-reacting immunologic material (CRIM) 
      were observed in control individuals. Decreased amounts of the same CRIM forms 
      were detected in most type 1 Gaucher disease patients, but single CRIM forms of 
      variable molecular weight were observed in several non-Jewish type 1 variants. 
      One or two CRIM forms of variable molecular weight were found in neuronopathic 
      (type 2 and type 3) patients. The amount of CRIM was severely decreased in the 
      majority of the type 2 and type 3 patients; one American black type 2 patient was 
      CRIM negative. With this one exception, one CRIM form was detected in the 
      cell-free culture media from all normal or Gaucher disease fibroblasts that had 
      an Mr approximately 2,000 greater than the highest respective intracellular 
      molecular-weight form. All intra- or extracellular CRIM forms were reduced to a 
      single form after deglycosylation with N-Glycanase. In addition, the 
      radioactivity from [3H]Br-conduritol B epoxide, a specific covalent inhibitor of 
      beta-Glc, localized to the CRIM forms of beta-Glc on immunoblots. These results 
      indicate that all subtypes and variants of Gaucher disease result from mutations 
      that alter the stability and/or processing of beta-Glc. Furthermore, the 
      heterogeneity of the CRIM patterns within and among the variants of Gaucher 
      disease cause the diagnostic usefulness of immunoblotting to be restricted to 
      those families in which the phenotype has been well established.
FAU - Fabbro, D
AU  - Fabbro D
FAU - Desnick, R J
AU  - Desnick RJ
FAU - Grabowski, G A
AU  - Grabowski GA
LA  - eng
GR  - K04 DK01351/DK/NIDDK NIH HHS/United States
GR  - R01-DK 36729/DK/NIDDK NIH HHS/United States
GR  - RR-71/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Antibodies, Monoclonal)
RN  - EC 3.2.1.- (Glucosidases)
RN  - EC 3.2.1.45 (Glucosylceramidase)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - Cells, Cultured
MH  - Fibroblasts/enzymology
MH  - Gaucher Disease/enzymology/*genetics
MH  - *Genetic Variation
MH  - Glucosidases/*analysis
MH  - Glucosylceramidase/*analysis/deficiency/immunology
MH  - Humans
MH  - Molecular Weight
MH  - Phenotype
MH  - Solubility
PMC - PMC1684010
EDAT- 1987/01/01 00:00
MHDA- 1987/01/01 00:01
PMCR- 1987/07/01
CRDT- 1987/01/01 00:00
PHST- 1987/01/01 00:00 [pubmed]
PHST- 1987/01/01 00:01 [medline]
PHST- 1987/01/01 00:00 [entrez]
PHST- 1987/07/01 00:00 [pmc-release]
PST - ppublish
SO  - Am J Hum Genet. 1987 Jan;40(1):15-31.