Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 14-year-old white girl with mild dysostosis multiplex, odontoid hypoplasia, short stature, cloudy corneas, keratansulfaturia, but without detectable central nervous system abnormalities was referred with the diagnosis of Morquio syndrome. Clinical and roentgenographic findings were minimal compared to those of typical patients with the Morquio syndrome, MPS IV. Beta-Galactosidase activity in extracts of the patient's cultured fibroblasts was deficient, while that of galactosamine-6-sulfate sulfatase was normal. Conjunctival biopsy revealed intracytoplasmic vacuoles typical of lysosomal storage diseases. It is postulated that in this patient the deficiency of a beta-galactosidase is responsible for inadequate degradation of keratan sulfate and the appearance of a mild form of the Morquio syndrome (MPS IVB).
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PMID:Morquio-like syndrome with beta galactosidase deficiency and normal hexosamine sulfatase activity: mucopolysacchariodosis IVB. 41 14

Human beta-galactosidase precursor mRNA is alternatively spliced into an abundant 2.5-kb transcript and a minor 2.0-kb species. These templates direct the synthesis of the classic lysosomal beta-D-galactosidase enzyme and of a beta-galactosidase-related protein with no enzymatic activity. Mutations in the beta-galactosidase gene result in the lysosomal storage disorders GM1-gangliosidosis and Morquio B syndrome. To analyze the genetic lesions underlying these syndromes we have isolated the human beta-galactosidase gene and determined its organization. The gene spans greater than 62.5 kb and contains 16 exons. Promoter activity is located on a 236-bp Pst I fragment which works in a direction-independent manner. A second Pst I fragment of 851 bp located upstream from the first negatively regulates initiation of transcription. The promoter has characteristics of a housekeeping gene with GC-rich stretches and five potential SP1 transcription elements on two strands. We identified multiple cap sites of the mRNA, the major of which maps 53 bp upstream from the translation initiation codon. The portion of the human pre-mRNA undergoing alternative splicing is encoded by exons II-VII. Sequence analysis of equivalent mouse exons showed an identical genomic organization. However, translation of the corresponding differentially spliced murine transcript is interrupted in its reading frame. Thus, the mouse gene cannot encode a beta-galactosidase-related protein in a manner similar to the human counterpart. Differential expression of the murine beta-galactosidase transcript is observed in different mouse tissues.
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PMID:Organization of the gene encoding human lysosomal beta-galactosidase. 190 71

Dental examinations on nine patients with mucopolysaccharidosis type IV A (MPS IV A, Morquio's disease type A) were carried out. Detailed medical, radiologic, and biochemical studies of each case were also performed independently. Dental changes were present in all cases, although the severity varied. The severity of the dental changes did not correlate with the clinical or biochemical findings in all cases. These dental changes are seen only in MPS IV A (N-acetylgalactosamine-6-sulphate sulphatase deficiency) and are not found in MPS IV B (beta-galactosidase deficiency) or the recently delineated MPS IV C (enzyme defect unknown). The dental changes can aid in the diagnosis of patients affected by MPS IV A and are especially useful in mild atypical cases.
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PMID:Dental findings in mucopolysaccharidosis type IV A (Morquio's disease type A). 212 90

To study the enzymatic properties of beta-galactosidase from the patients with a beta-galactosidase deficiency such as GM1 gangliosidosis, determination of enzymatic activity with naturally occurring substrates, asialofetuin in addition to another natural substrate, GM1 ganglioside, is essentially required. With a previously reported, simple and sensitive fluorometric assay for GM1 ganglioside beta-galactosidase using high performance liquid chromatography (HPLC), optimal reaction conditions were determined for the assay of acid beta-galactosidase activity toward asialofetuin in skin fibroblast homogenates. Under these conditions, reduced enzymatic activities could be detected in cultured skin fibroblasts from patients with type 1 and 3 GM1 gangliosidoses and mucopolysaccharidosis IV-B (Morquio B syndrome). This method was applicable to study of the enzymatic properties of the mutant beta-galactosidase and provided an alternative to assays employing radioactive or artificial substrates.
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PMID:A microassay for acid beta-galactosidase activity toward asialofetuin. 241 73

We have isolated two cDNAs encoding human lysosomal beta-galactosidase, the enzyme deficient in GM1-gangliosidosis and Morquio B syndrome, and a beta-galactosidase-related protein. In total RNA from normal fibroblasts a major mRNA of about 2.5 kilobases (kb) is recognized by cDNA probes. A minor transcript of about 2.0 kb is visible only in immunoselected polysomal RNA. A heterogeneous pattern of expression of the 2.5-kb beta-galactosidase transcript is observed in fibroblasts from different GM1-gangliosidosis patients. The nucleotide sequences of the two cDNAs are extensively colinear. However, the short cDNA misses two noncontiguous protein-encoding regions (1 and 2) present in the long cDNA. The exclusion of region 1 in the short molecule introduces a frameshift in its 3'-flanking sequence, which is restored by the exclusion of region 2. These findings imply the existence of two mRNA templates, which are read in a different frame only in the nucleotide stretch between regions 1 and 2. Sequence analysis of genomic exons of the beta-galactosidase gene shows that the short mRNA is generated by alternative splicing. The long and short cDNAs direct the synthesis in COS-1 cells of beta-galactosidase polypeptides of 85 and 68 kDa, respectively. Only the long protein is catalytically active under the assay conditions used, and it is capable of correcting beta-galactosidase activity after endocytosis by GM1-gangliosidosis fibroblasts. The subcellular localization of cDNA-encoded beta-galactosidase and beta-galactosidase-related proteins is different.
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PMID:Alternative splicing of beta-galactosidase mRNA generates the classic lysosomal enzyme and a beta-galactosidase-related protein. 251 Dec 8

We studied beta-galactosidase in skin fibroblasts from patients with different forms of beta-galactosidase deficiency: adult GM1 gangliosidosis, type 1 GM1 gangliosidosis, and Morquio B syndrome. Enzyme properties in the adult cases differed from the other disorders and also from normal controls. Genetic hybridization studies indicated that all three forms belong to the same complementation group. Therefore, the adult disorder must be due to a mutation of the structural gene for beta-galactosidase, which is allelic to the mutations in type 1 GM1 gangliosidosis and Morquio B syndrome.
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PMID:Atypical adult GM1 gangliosidosis: biochemical comparison with other forms of primary beta-galactosidase deficiency. 309 33

Typical dental changes were present in all cases, although they were of variable degree. However, the tooth morphology would appear to be highly specific for MPS IV A, and is not found in MPS IV B (beta-galactosidase deficiency) or the recently delineated MPS IV C (enzyme defect unknown). Thus the dental changes have a very useful diagnostic potential in mild atypical cases of MPS IV A, although they may only be demonstrable radiologically in some such cases.
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PMID:Clinical findings in 12 patients with MPS IV A (Morquio's disease). Further evidence for heterogeneity. Part II: Dental findings. 312 22

Fibroblasts from patients with Morquio B syndrome contain normal numbers of beta-galactosidase molecules with normal turnover but strongly reduced activity per enzyme molecule. Various substrate affinities are abnormal: the Km for methylum belliferyl (MU)-beta-galactoside is 4-10-fold elevated and affinity for keratan sulphate and oligosaccharides, isolated from Morquio B urine, was not detectable. In contrast, these substrate affinities are normal for beta-galactosidase in adult type GM1-gangliosidosis fibroblasts. Cell hybridization studies demonstrate that Morquio B syndrome and infantile and adult type GM1-gangliosidosis belong to the same complementation group. From these results we conclude that Morquio B syndrome is caused by a mutation in the structural gene for beta-galactosidase, which is allelic to the mutations in infantile and adult type GM1-gangliosidosis. Urinary excretion of keratan sulphate and oligosaccharides is abnormal in Morquio B syndrome but normal in adult type GM1-gangliosidosis. The catalytic properties of beta-galactosidase in Morquio B syndrome and GM1-gangliosidosis provide a possible explanation for the distinct clinical manifestations in these disorders.
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PMID:Morquio B syndrome: a primary defect in beta-galactosidase. 641 7

The nature of the molecular defect resulting in the beta-galactosidase deficiency in different forms of GM1-gangliosidosis and mucopolysaccharidosis IV B (Morquio B syndrome) was investigated. Normal and mutant cultured skin fibroblasts were labeled in vivo with [3H]leucine and immunoprecipitation studies with human anti-beta-galactosidase antiserum were performed, followed by polyacrylamide gel electrophoresis and fluorography. In Morquio B syndrome, the mutation does not interfere with the normal processing and intralysosomal aggregation of beta-galactosidase. In cells from infantile and adult GM1-gangliosidosis, 85-kDa precursor beta-galactosidase was found to be synthesized normally but more than 90% of the enzyme was subsequently degraded at one of the early steps in posttranslational processing. The residual 5-10% beta-galactosidase activity in adult GM1-gangliosidosis is 64-kDa mature lysosomal enzyme with normal catalytic properties but with a reduced ability of the monomeric form to aggregate into high molecular weight multimers. Knowledge of the exact nature of the molecular defect underlying beta-galactosidase deficiency in man may lead to a better understanding of the clinical and pathological heterogeneity among patients with different types of GM1-gangliosidosis and Morquio B syndrome.
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PMID:Processing of human beta-galactosidase in GM1-gangliosidosis and Morquio B syndrome. 642 Apr 16

GM1 gangliosidosis and Morquio syndrome type B (MPS IVB) are inherited lyosomal storage disorders associated with deficiency of beta-galactosidase-A (beta GALA) activity. A recombinant plasmid containing a biotinylated cDNA (2.4-kb insert) encoding human beta GALA was used to localize the enzyme locus by fluorescence in situ hybridization (FISH). The human beta GALA gene was assigned to 3p21.33 by FISH.
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PMID:Assignment of human beta-galactosidase-A gene to 3p21.33 by fluorescence in situ hybridization. 769 77


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