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Novel mutations in type 2 Gaucher disease in Chinese and their functional characterization by heterologous expression
Author(s) -
Tang Nelson L.S.,
Zhang Weimin,
Grabowski G.A.,
To K.F.,
Choy Francis Y.M.,
Ma S.L.,
Shi H.P.
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9348
Subject(s) - biology , genetics , mutation , gene , glucocerebrosidase , genome instability , dna , dna damage
We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and performed ex vivo expression for the novel mutations to characterize their functional defects. These patients were diagnosed by enzymatic assays and clinicopathologic features over the past five years in a national centre in China. Genomic DNA was sequenced by a two‐stage PCR approach for mutations in the functional GBA gene. Novel mutations were expressed with baculovirus‐transfected Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L, Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated clustering of type 2 mutations in three regions of the GBA gene. Expression of novel mutations revealed that the enzyme defect could arise from one of two mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability (P122L and N382K). © 2005 Wiley‐Liss, Inc.