title: A novel frame shift mutation in the PQBP1 gene identified in a Tunisian family with X-linked mental retardation.
abstract: Mental retardation (MR) is the most frequent cause of serious handicap in children and young adults. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Linkage studies followed by mutational analysis of known X-chromosomal genes related to mental retardation (MRX genes) localized within defined genetic intervals represent a rational strategy to identify a genetic cause of the disorder. Here, we report a Tunisian family including 3 males with severe to mild mental retardation, short stature, lean body and microcephaly; we mapped the disease to a unique interval encompassing Xp21.1-Xq21.33 (with a maximum LOD score of 0.90). Subsequent mutation analysis of genes located in this interval allowed us to identify a truncating mutation in the PQBP1 gene. This mutation is an insertion of an adenosine residue in exon 5 (c.631insA). This frameshift insertion causes premature stop codon at amino acid position 226. The observed mutation was found in all males with MR in this family. Together with previously reported observations, our data further confirm that PQBP1 gene should be tested for males showing mental retardation, short stature, lean body and microcephaly.
authors.affiliation: Laboratoire de Génétique Humaine, Faculté de Médecine de Tunis, 15 Jebel Lakhdhar LaRabta, Tunis 1007, Tunisia. imen_rejeb@yahoo.fr
authors.forename: Imen
authors.initials: I
authors.lastname: Rejeb
authors.forename: Lamia
authors.initials: L
authors.lastname: Ben Jemaa
authors.forename: Leila
authors.initials: L
authors.lastname: Abaied
authors.forename: Lilia
authors.initials: L
authors.lastname: Kraoua
authors.forename: Yoann
authors.initials: Y
authors.lastname: Saillour
authors.forename: Faouzi
authors.initials: F
authors.lastname: Maazoul
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Habiba
authors.initials: H
authors.lastname: Chaabouni
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006130:Growth Disorders / Q000473:pathology; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008831:Microcephaly / Q000473:pathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D014416:Tunisia
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human