Identification of a novel recombinant allele in three unrelated Italian Gaucher patients: Implications for prognosis and genetic counseling

Gaucher disease (GD) results from deleterious mutations in the glucocerebro sidase gene. The relatively high frequency of some of these, especially at cDNA nucleotide 1226G (N370S) and at cDNA nucleotide 1448C (LA44P), has led to the development of rapid screening techniques that can sometimes be mis leading. In this report, we describe a novel rearrangement between the gluc ocerebrosidase gene and its pseudogene, identified as a consequence of a di screpancy between the genotype, homozygous for the common 1226G mutation, o f an Italian patient with type 1 Gaucher disease, and the absence of the 12 26G allele in her daughter. Additional investigations went on to reveal a n ovel recombinant allele beginning in intron 6 and extending through the res t of the coding sequence. Italian GD patients found homozygous for a specif ic mutation or with one or both alleles still unknown were further investig ated and the novel recombinant allele was identified in an adult type 1 pat ient previously genotyped 1226G/1226G and in a young patient with an unknow n genotype. The detection of this allele in three unrelated GD patients ori ginating from the same geographic area in central Italy suggested a founder effect. This study emphasizes the implications of an accurate genotyping f or the prognostic value of glucocerebrosidase genotype and reliable genetic counseling, (C) 2000 Academic Press.