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Gaucher disease is the most common lysosomal storage disorder, it results from the inherited deficiency of the enzyme glucocerebrosidase, the accumulation of its substrate causes many clinical manifestations. Since the discovery of GBA gene, more than 200 different mutations have been identified, but only handful mutations are recurrent (N370S, L444P and c.84insG). In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in ten unrelated Tunisian children with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing, has shown that N370S is the most frequent mutation (6/20 mutant alleles, 30%), followed by recombinant allele (RecNciI) which is found in five patients (5/20 mutant alleles, 25%), the L444P mutation represent 20% (4/20 mutant alleles). Our findings revealed that five among ten studied patients, were compound heterozygous N370S/RecNciI (50%). The screening of these mutations provides a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allows also genetic counselling for their family members.

In the Portuguese population the most frequent form of Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles. The frequency of this mutation was accurately determined in the Portuguese population, which does not present an Ashkenazi Jewish genetic background. A gene frequency of 0.0043, with 95% confidence limits between 0.0023 and 0.0063, was obtained studying the genomic DNA of 2000 blood cards randomly sampled from the national neonatal screening program. On the basis of this frequency a significantly high number of homozygotes for the N370S mutation should be expected in the Portuguese population. This finding supports the idea that the majority of homozygotes for this mutation present a very mild clinical phenotype and remain undiagnosed.

Reliable estimates of the frequency of Gaucher disease-producing mutations are not available. The high frequency of Gaucher disease in the Ashkenazi Jewish population is due to the occurrence of a mutation at nucleotide (nt) 1226. We have screened 593 DNA samples from normal Ashkenazi Jews, as well as 62 DNA samples from all our Ashkenazi Jewish patients with Gaucher disease, for the presence of the 1226 mutation. In the 593 presumed normal Ashkenazi Jewish individuals the 1226 mutation was identified in the heterozygous state in 37 and in the homozygous state in two, giving a gene frequency of .035 for the mutation. This 1226 mutation represented 73% of the 124 Gaucher disease alleles in Jewish Gaucher disease patients. Accordingly we estimate that the gene frequency for Gaucher disease among the Ashkenazi Jewish population is .047, which is equivalent to a carrier frequency of 8.9% and a birth incidence of 1:450.

A study of 30 Swedish families with the Norrbottnian type of Gaucher disease provides evidence for two clusters of the gene, one close to Overkalix in the northern part of the county of Norrbotten and the other in the vicinity of Arvidsjaur in the southern part of the same county. The gene for Gaucher disease in Overkalix appeared later than that in Arvidsjaur. A founder moving from Arvidsjaur to Overkalix during the seventeenth century or two different mutations are the most likely explanations of this finding.