Beta-galactosidase deficiencies and novel GLB1 mutations in three Chinese patients with Morquio B disease or GM1 ganglio
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Beta-galactosidase deficiencies and novel GLB1 mutations in three Chinese patients with Morquio B disease or GM1 gangliosidosis Hong-Lin Lei, Jun Ye, Wen-Juan Qiu, Hui-Wen Zhang, Lian-Shu Han, Yu Wang, Xue-Fan Gu Shanghai, China Background: This paper aims to report GLB1 activities and mutation analysis of three patients from the mainland of China, one with Morquio B disease and two with GM1 gangliosidosis.
Results: The enzymatic activity of GLB1 was found to be 5.03, 4.20, and 4.50 nmol/h/mg in the three patients, respectively. Patient 1 was a compound heterozygote for p.[Arg148Cys] and p.[Tyr485Cys] mutations in the GLB1 gene. Patient 2 was a compound heterozygote for p.[Tyr270Phe] and p.[Leu337Pro] mutations. Patient 3 was a homozygote for p.[Asp448Val] mutation. Three mutations (p.[Tyr485Cys], p.[Tyr270Phe] and p.[Leu337Pro]) were novel variants and were predicted to damage GLB1 function. Conclusions: The enzymatic activity and related gene analysis of β-galactosidase should be performed in clinically suspected individuals to confirm diagnosis. The three novel mutations, p.[Tyr485Cys], p.[Tyr270Phe], and p.[Leu337Pro], are thought to be disease-causing mutations. World J Pediatr 2012;8(4):359-362
Author Affiliations: Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (Lei HL, Ye J, Qiu WJ, Zhang HW, Han LS, Wang Y, Gu XF) Corresponding Author: Jun Ye, MD, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China (Tel: 86-2125076455; Fax: 86-21-65791316; Email: [email protected]) doi: 10.1007/s12519-012-0382-0 ©Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2012. All rights reserved.
Brief report
Methods: GLB1 activity and GLB1 gene mutation were analyzed in the three patients who were clinically suspected of having Morquio B disease or GM1 gangliosidosis. Novel mutations were analyzed by aligning GLB1 homologs, 100 control chromosomes, and the PolyPhen-2 tool.
Key words: β-galactosidase; enzyme assays; GM1 gangliosidosis; Morquio B disease; mutation analysis
Introduction
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M1 gangliosidosis (MIM# 230500) and Morquio B disease (MIM# 253010) are autosomal recessive lysosomal storage disorders (LSDs) caused by deficiency of lysosomal β-galactosidase (GLB1; EC 3.2.1.23) due to mutations in the GLB1 gene. GLB1 deficiency leads to accumulation of ganglioside GM1 and keratan sulfate.[1,2] The estimated incidence of GM1 gangliosidosis is 1 in 100 000-200 000 live births. [3] GM1 gangliosidosis has been classified into three major clinical forms. [4] The infantile form is the most severe one, which is characterized by rapid psychomotor deterioration beginning within three to six months of birth, skeletal dysplasia, and death typically within 24 months of age. The Morquio B disease is rare and characterized by shor
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