title: Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease.
abstract: A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early-onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect.
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia; Biochemistry and Molecular Biology Laboratory, Children's Hospital, Tunis, Tunisia. Electronic address: achouriafef@yahoo.fr.
authors.forename: Afef
authors.initials: A
authors.lastname: Achouri-Rassas
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ben Ali
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Fray
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Children's Hospital, Tunis, Tunisia.
authors.forename: Sondes
authors.initials: S
authors.lastname: Hadj Fredj
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Meriem
authors.initials: M
authors.lastname: Kechaou
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Nouria Oudiaa
authors.initials: NO
authors.lastname: Zakraoui
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Aroua
authors.initials: A
authors.lastname: Cherif
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Slim
authors.initials: S
authors.lastname: Chabbi
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Anane
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Children's Hospital, Tunis, Tunisia.
authors.forename: Taieb
authors.initials: T
authors.lastname: Messaoud
authors.affiliation: Neurological Department, Razi Hospital, Tunis, Tunisia.
authors.forename: Riadh
authors.initials: R
authors.lastname: Gouider
authors.affiliation: Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Samir
authors.initials: S
authors.lastname: Belal
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D053764:Presenilin-1 / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014416:Tunisia
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1; D007532:Isoleucine; D013912:Threonine
keywords: Early-onset Alzheimer's disease; PSEN 1 mutation; Tunisian family