A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher's Disease.
BACKGROUND
Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid β-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This study aimed to discover more mutations and provide data for the genetic pattern of the gene, which will help the development of quick and accurate genetic diagnostic tools for this disease.


METHODS
Genomic DNA was obtained from peripheral blood leukocytes of the patient and Sanger sequencing is used to sequence GBA gene. Sequence alignments of mammalian β-GBA (GCase) and three-dimensional protein structure prediction of the mutation were made. A construct of this mutant and its compound heterozygous counterpart were used to measure GCase in vitro.


RESULTS
GCase is relatively conserved at p.T219A. This novel mutation differs from its wild-type in structure. Moreover, it also causes a reduction in GCase enzyme activity.


CONCLUSIONS
This novel mutation (c.655A>G, p.T219A) is a pathogenic missense mutation, which contributes to GD.
Lin-Yu
LY
Liu
Fei
F
Liu
Si-Chen
SC
Du
Sha-Yi
SY
Jiang
Hui-Jun
HJ
Wang
Jin
J
Zhang
Wei
W
Wang
Department of Biochemistry and Molecular Biology, Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Institute of Medical Sciences, Fudan University, Shanghai 200032; Shanghai Institute of Medical Genetics, Children's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200032, China.
Duan
D
Ma
D002675:Child, Preschool; D005776:Gaucher Disease / Q000235:genetics*; D005962:Glucosylceramidase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA
D005962:Glucosylceramidase