title: Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients.
abstract: Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is a genetically heterogeneous developmental disorder. The X-linked form of AAS has been ascribed to mutations in the FGD1 gene. However, although AAS may be considered as a relatively frequent clinical diagnosis, mutations have been established in few patients. Genetic heterogeneity and the clinical overlap with a number of other syndromes might explain this discrepancy. In this study, we have conducted a single-strand conformation polymorphism (SSCP) analysis of the entire coding region of FGD1 in 46 AAS patients and identified eight novel mutations, including one insertion, four deletions and three missense mutations (19.56% detection rate). One mutation (528insC) was found in two independent families. The mutations are scattered all along the coding sequence. Phenotypically, all affected males present with the characteristic AAS phenotype. FGD1 mutations were not associated with severe mental retardation. However, neuropsychiatric disorders, mainly behavioural and learning problems in childhood, were observed in five out of 12 mutated individuals. The current study provides further evidence that mutations of FGD1 may cause AAS and expands the spectrum of disease-causing mutations. The importance of considering the neuropsychological phenotype of AAS patients is discussed.
authors.affiliation: Molecular Medicine, Azienda Ospedaliera Universitaria Senese, Siena, Italy. a.orrico@ao-siena.toscana.it
authors.forename: Alfredo
authors.initials: A
authors.lastname: Orrico
authors.forename: Lucia
authors.initials: L
authors.lastname: Galli
authors.forename: Maria Luigia
authors.initials: ML
authors.lastname: Cavaliere
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Ellen
authors.initials: E
authors.lastname: Crushell
authors.forename: Maria Michela
authors.initials: MM
authors.lastname: Rinaldi
authors.forename: Ana
authors.initials: A
authors.lastname: Medeira
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sorrentino
mesh_terms: D000293:Adolescent; D000328:Adult; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D014564:Urogenital Abnormalities / Q000235:genetics
chemical_list: C490796:FGD1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins