GM01602

GM01602 Fibroblast

Description:

MUCOPOLYSACCHARIDOSIS TYPE IVB
GANGLIOSIDOSIS, GENERALIZED GM1, TYPE I
GALACTOSIDASE, BETA-1; GLB1

Affected:

Yes

Sex:

Female

Age:

11 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Carbohydrate Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Normal level of N-acetylgalactosamine 6 sulfate sulfatase; less than 4% of control B-galactosidase activity using either 4MU-B-gal or GM1 ganglioside; similarly affected sister; donor subject is a compound heterozygote with two mutations in the GLB1 gene: Trp273Leu (W273L)/Arg482His (R482H)

Characterizations

PDL at Freeze

3.92

beta-galactosidase

Giugliani et al (Clin Genet 32:313-325 1987) assayed B-galactosidase activity in this fibroblast culture using 4-methylumbelliferyl B-Dgalactoside and with the alternative artificial substrates: 4MU B-Dfucoside and 4MU A-L-arabinoside. Deficient enzyme activity towards all of these substrates was observed. The respective observed values were 7.2% 2.6% and 1.2% of normal control activities. Oshima et al (Am J Hum Genet 49:1091-1093 1991) reported that DNA from this Morquio B disease patient had 2 mutations in the B-galactosidase gene: Trp-273>Leu and Arg-482>His. EC Number: 3.2.1.23; <7% activity.

beta-glucuronidase

Giugliani et al (Clin Genet 32:313-325 1987) assayed B-glucuronidase activity in this type IVB Morquio syndrome cell culture and observed normal B-glucuronidase enzyme activity levels. EC Number: 3.2.1.31

beta-galactosidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.23; 4% activity.

Gene

GLB1

Chromosomal Location

3p22.3

Allelic Variant 1

611458.0009; MUCOPOLYSACCHARIDOSIS, TYPE IVB

Identified Mutation

TRP273LEU; In 3 affected individuals from 2 unrelated families with Morquio syndrome B (MPS4B; 253010), also known as mucopolysaccharidosis type IVB, Oshima et al. (1991) identified compound heterozygosity for 2 mutations in the GLB1 gene. All patients shared a heterozygous 851-852TG-CT change, resulting in a trp273-to-leu (W273L) substitution, and another pathogenic change (R482H, 611458.0010 and W509C, 611458.0011, respectively). The W273L mutant showed 8% residual enzyme activity, but the other mutations expressed no detectable enzyme activity.

Gene

GLB1

Chromosomal Location

3p22.3

Allelic Variant 2

611458.0010; MUCOPOLYSACCHARIDOSIS TYPE IVB

Identified Mutation

ARG482HIS

Phenotypic Data

Remarks

Publications

Pshezhetsky AV, Potier M, Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate. J Biol Chem271:28359-65 1996

PubMed ID: 8910459

Oshima A, Yoshida K, Shimmoto M, Fukuhara Y, Sakuraba H, Suzuki Y, Human beta-galactosidase gene mutations in morquio B disease. Am J Hum Genet49:1091-3 1991

PubMed ID: 1928092

Ahern-Rindell AJ, Murnane RD, Prieur DJ, Interspecific genetic complementation analysis of human and sheep fibroblasts with beta-galactosidase deficiency. Somat Cell Mol Genet15:525-33 1989

PubMed ID: 2512653

Giugliani R, Jackson M, Skinner SJ, Vimal CM, Fensom AH, Fahmy N, Sjovall A, Benson PF, Progressive mental regression in siblings with Morquio disease type B (mucopolysaccharidosis IV B). Clin Genet32:313-25 1987

PubMed ID: 3121219

Kobayashi T, Shinnoh N, Kuroiwa Y, Incorporation and degradation of GM1 ganglioside and asialoGM1 ganglioside in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency. Biochim Biophys Acta875:115-21 1986

PubMed ID: 3079639