title: Deletion of arginine (608) in acid sphingomyelinase is the prevalent mutation among Niemann-Pick disease type B patients from northern Africa.
abstract: There is a high incidence of Niemann-Pick type B disease in the Maghreb 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 acid residue 608 was found in one patient. The same mutation was also observed in another of our cases. An original screening procedure using 3'-end digoxigenin-labeled allele-specific oligonucleotides and chemiluminescent detection was developed and used parallel to the conventional assay with 5'-end radiolabeled oligonucleotides. Of the 15 non-related, non-Jewish North African type B patients studied, 12 were homozygous and two compound heterozygous for this deletion (26 delta R608 alleles/30 mutant alleles). Among type B patients from other geographic regions (France, UK, Italy, Czechoslovakia), this mutation was observed in only one of the 16 alleles studied. Our results indicate that deletion of arginine 608 in the acid sphingomyelinase gene is the highly prevalent mutation underlying Niemann-Pick type B disease in the population of Maghreb. A varying severity of the clinical and enzymatic expression within the non-neuronopathic phenotype has however been observed in patients homozygous for the mutation.
authors.affiliation: Département de Biochimie, INSERM U189, Faculté de Médecine Lyon-Sud, Oullins, France.
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
authors.forename: K
authors.initials: K
authors.lastname: Ferlinz
authors.forename: R
authors.initials: R
authors.lastname: Rousson
authors.forename: S
authors.initials: S
authors.lastname: Duthel
authors.forename: P
authors.initials: P
authors.lastname: Louisot
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000352:Africa, Northern / Q000453:epidemiology; D000483:Alleles; D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000235:genetics; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D003062:Codon; D004247:DNA / Q000032:analysis; D005347:Fibroblasts; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009542:Niemann-Pick Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015345:Oligonucleotide Probes; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: D003062:Codon; D015345:Oligonucleotide Probes; D004247:DNA; D001120:Arginine; D013108:Sphingomyelin Phosphodiesterase