- 作者: Chi-Fan Yang; Jer-Yuarn Wu; Fuu-Jen Tsai
- 作者服務機構: Institute of Biomedical Sciences, Academia Sinica, Academia Road, Nankang, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease
caused by deficiency of acid beta-galactosidase (GLB1; EC3.2.1.23). Here, we identify three
novel mutations in the GLB1 gene from two Han Chinese patients with GM1 that appear
correlated with clinical phenotype.
Methods: One of the two Han Chinese patients with GM1 presented with the juvenile form,
and the other with the infantile form with cardiac involvement. Sequencing of the entire GLB1
gene revealed three novel mutations (p.H102D, p.G494V, c.495_497delTCT), 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.
Results: The first case (patient 1) with the juvenile form contained two missense mutations,
p.H102D and p.A301V. Patient 2 diagnosed with the infantile form of the disease with cardiac
involvement was compound heterozygous for p.G494V and c.495_497delTCT mutations. All
mutant beta-galactosidases exhibited significantly reduced activity (12%, 0%, 0%, and 0% for
p.H102D, p.A301V, p.G494V, and c.495_497delTCT), compared with the wild-type betagalactosidase
cDNA clone. The mutations identified in patient 2 with cardiomyopathy were
localized in the GLB1 gene region common to both lysosomal beta-galactosidase and elastin
binding protein (EBP), and caused a deletion in the elastin-binding domain of EBP.
Conclusions: All four mutations identified in Han Chinese patients induce significant
suppression of β-galactosidase activity, correlating with severity of disease and presence of
cardiomyopathy. - 中文關鍵字: --
- 英文關鍵字: --