Detection of three rare (G377S, T134P and 1451delAC), and two novel mutations (G195W and Rec[1263del55;1342G>C]] in Spanish Gaucher disease patients. Mutation in brief no. 251. Online.

To study glucocerebrosidase mutations causing Gaucher disease, we have screened 30 apparently unrelated patients for the presence of 7 previous described mutations. N370S (1226A>G) was the most common mutation (43%), followed by L444P (1448T>C) (23%). To identify the other unknown mutations, we screened regions of the glucocerebrosidase gene (GBA), by SSCP and sequencing. These analyses allowed identification of one novel G195W (700G>T), and two rare T134P (517A>C) and G377S (1246G>A) missense mutations. Mutation T134P (517A>C) was present in a type I patient, while G195W (700G>T), was encountered in two patients (types I, and III). The prevalence of mutation G377S (1246G>A), previously undetected in Spain, was found to be high (8%) making it a good candidate for routine genetic screening in patients from Spanish descent. Two null mutations have been identified as well Rec[1263del55;1342G>C], and 1451delAC). The Rec[1263del55;1342G>C] is a novel chimeric allele in which the gene sequence between nucleotides 5878-6272 [sequence numbering according to Horowitz et al.(1989)] has been replaced by the homologous region of the pseudogene, and consequently it carries the 1263del55 and D409H (1342G>C) mutations. The functional equivalence of this allele to a 1263del55 allele previously described, suggest the potencial existence of a group of four distinct 55 bp deletion harboring alleles with identical clinical consequences.