title: Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene.
abstract: Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice site mutation (c.1935+3A>C). A recurrent mutation (p.R656X) was detected in three independent families. We did not find any evidence for phenotype-genotype correlations between type and position of mutations and clinical features. In addition to the well-established phenotypic features of AAS, other clinical features are also reported and discussed.
authors.affiliation: Medicina Molecolare, Azienda Ospedaliera Universitaria Senese, Siena, Italy. a.orrico@ao-siena.toscana.it
authors.forename: A
authors.initials: A
authors.lastname: Orrico
authors.forename: L
authors.initials: L
authors.lastname: Galli
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.forename: J
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: S M
authors.initials: SM
authors.lastname: Azzarello-Burri
authors.forename: J M
authors.initials: JM
authors.lastname: Hertz
authors.forename: S
authors.initials: S
authors.lastname: Jacquemont
authors.forename: R
authors.initials: R
authors.lastname: Taurisano
authors.forename: I
authors.initials: I
authors.lastname: Arroyo Carrera
authors.forename: E
authors.initials: E
authors.lastname: Tarantino
authors.forename: K
authors.initials: K
authors.lastname: Devriendt
authors.forename: D
authors.initials: D
authors.lastname: Melis
authors.forename: T
authors.initials: T
authors.lastname: Thelle
authors.forename: U
authors.initials: U
authors.lastname: Meinhardt
authors.forename: V
authors.initials: V
authors.lastname: Sorrentino
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D020816:Amino Acid Motifs; D001842:Bone and Bones / Q000002:abnormalities; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005060:Europe; D005837:Genitalia, Male / Q000002:abnormalities; D018095:Germ-Line Mutation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D013577:Syndrome
chemical_list: C490796:FGD1 protein, human; D020662:Guanine Nucleotide Exchange Factors