Three novel beta-galactosidase gene mutations in Han Chinese patients with GM1 gangliosidosis are correlated with disease severity.

[gm1 gangliosidosis]

GM 1 gangliosidosis (GM 1 ) is an autosomal recessive lysosomal storage disease caused by deficiency of acid beta -galactosidase (GLB 1 ; EC 3 .2 .1 .23 ). Here , we identify three novel mutations in the GLB 1 gene from two Han Chinese patients with GM 1 that appear correlated with clinical phenotype .One of the two Han Chinese patients with GM 1 presented with the juvenile form , and the other with the infantile form with cardiac involvement . Sequencing of the entire GLB 1 gene revealed three novel mutations (p .H 102 D , p .G 494 V , c .495 _497 delTCT ), which were absent in 94 normal controls . Transient expression of cDNA encoding these variants was performed in COS -1 cells to evaluate β-galactosidase activities .The first case (patient 1 ) with the juvenile form contained two missense mutations , p .H 102 D and p .A 301 V . Patient 2 diagnosed with the infantile form of the disease with cardiac involvement was compound heterozygous for p .G 494 V and c .495 _497 delTCT mutations . All mutant beta -galactosidases exhibited significantly reduced activity (12 %, 0 %, 0 %, and 0 % for p .H 102 D , p .A 301 V , p .G 494 V , and c .495 _497 delTCT ), compared with the wild-type beta -galactosidase cDNA clone . The mutations identified in patient 2 with cardiomyopathy were localized in the GLB 1 gene region common to both lysosomal beta -galactosidase and elastin binding protein (EBP ), and caused a deletion in the elastin -binding domain of EBP .A ll four mutations identified in Han Chinese patients induce significant suppression of β-galactosidase activity , correlating with severity of disease and presence of cardiomyopathy .

Diseases
Validation

Diseases presenting "first case" symptom

achondroplasia

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

carcinoma of the gallbladder

child syndrome

cholangiocarcinoma

classical phenylketonuria

coats disease

cohen syndrome

congenital toxoplasmosis

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dentin dysplasia

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

esophageal adenocarcinoma

esophageal carcinoma

fabry disease

familial mediterranean fever

focal myositis

gm1 gangliosidosis

harlequin ichthyosis

hodgkin lymphoma, classical

homocystinuria without methylmalonic aciduria

junctional epidermolysis bullosa

kabuki syndrome

krabbe disease

lamellar ichthyosis

legionellosis

liposarcoma

locked-in syndrome

malignant atrophic papulosis

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

primary hyperoxaluria type 1

proteus syndrome

pyomyositis

systemic capillary leak syndrome

thoracic outlet syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

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