DELETION OF ARGININE (608) IN ACID SPHINGOMYELINASE IS THE PREVALENT MUTATION AMONG NIEMANN-PICK DISEASE TYPE-B PATIENTS FROM NORTHERN AFRICA

There is a high incidence of Niemann-Pick type B disease in the Maghre b region of North Africa, which includes Morocco, Algeria and Tunisia. A hypothesis that there may well be a common, predominant mutant acid sphingomyelinase allele responsible for the type B phenotype in this population has been tested. A deletion of an arginine codon at amino a cid residue 608 was found in one patient. The same mutation was also o bserved in another of our cases. An original screening procedure using 3'-end digoxigenin-labeled allele-specific oligonucleotides and chemi luminescent detection was developed and used parallel to, the conventi onal assay with 5'-end radiolabeled oligonucleotides. Of the 15 non-re lated, non-Jewish North African type B patients studied, 12 were homoz ygous and two compound heterozygous for this deletion (26 DELTAR608 al leles/30 mutant alleles). Among type B patients from other geographic regions (France, UK, Italy, Czechoslovakia), this mutation was observe d in only one of the 16 alleles studied. Our results indicate that del etion of arginine 608 in the acid sphingomyelinase gene is the highly prevalent mutation underlying Niemann-Pick type B disease in the popul ation of Maghreb. A varying severity of the clinical and enzymatic exp ression within the non-neuronopathic phenotype has however been observ ed in patients homozygous for the mutation.