title: Ataxia-telangiectasia: founder effect among north African Jews.
abstract: The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition. A-T carriers were reported to be moderately cancer-prone. A wide variety of A-T mutations, most of which are unique to single families, were identified in various ethnic groups, precluding carrier screening with mutation-specific assays. However, a single mutation was observed in 32/33 defective ATM alleles in Jewish A-T families of North African origin, coming from various regions of Morocco and Tunisia. This mutation, 103C-->T, results in a stop codon at position 35 of the ATM protein. In keeping with the nature of this mutation, various antibodies directed against the ATM protein failed to defect this protein in patient cells. A rapid carrier detection assay detected this mutation in three out of 488 ATM alleles of Jewish Moroccan or Tunisian origin. This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Gilad
authors.forename: A
authors.initials: A
authors.lastname: Bar-Shira
authors.forename: R
authors.initials: R
authors.lastname: Harnik
authors.forename: D
authors.initials: D
authors.lastname: Shkedy
authors.forename: Y
authors.initials: Y
authors.lastname: Ziv
authors.forename: R
authors.initials: R
authors.lastname: Khosravi
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: L
authors.initials: L
authors.lastname: Vanagaite
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Frydman
authors.forename: M F
authors.initials: MF
authors.lastname: Lavin
authors.forename: D
authors.initials: D
authors.lastname: Hill
authors.forename: D A
authors.initials: DA
authors.lastname: Tagle
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
mesh_terms: D000352:Africa, Northern / Q000208:ethnology; D001260:Ataxia Telangiectasia / Q000208:ethnology* / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006801:Humans; D007585:Jews; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases