1. A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome)
- Author
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Maria Luigia Cavaliere, Lucia Galli, Alfredo Orrico, Vincenzo Sorrentino, Andrea Musacchio, Michela Falciani, Maria Michela Rinaldi, and Martina Bracci
- Subjects
Male ,Genetic Linkage ,DNA Mutational Analysis ,FGD1 gene ,Biochemistry ,Exon ,Structural Biology ,FGD1 ,Missense mutation ,Guanine Nucleotide Exchange Factors ,genetics ,Aarskog–Scott syndrome ,Child ,Conserved Sequence ,Polymorphism, Single-Stranded Conformational ,Genetics ,Single-Stranded Conformational ,Blood Proteins ,Exons ,Syndrome ,Aarskog–Scott disease ,Pleckstrin homology domain ,Pedigree ,Phenotype ,Italy ,Child, Preschool ,Female ,Guanine nucleotide exchange factor ,Abnormalities ,Multiple ,Biologie ,Protein Structure ,X Chromosome ,Molecular Sequence Data ,Biophysics ,Biology ,chemistry ,Genetic Heterogeneity ,medicine ,Bruton's tyrosine kinase ,Humans ,Abnormalities, Multiple ,Amino Acid Sequence ,Polymorphism ,Preschool ,chemistry/genetics/metabolism ,Molecular Biology ,Gene ,genetics, Amino Acid Sequence, Amino Acid Substitution ,genetics, Binding Sites, Blood Proteins ,chemistry, Child ,Preschool, Conserved Sequence ,genetics, DNA Mutational Analysis, Exons ,genetics, Female, Genetic Heterogeneity, Genetic Linkage ,genetics, Guanine Nucleotide Exchange Factors, Humans, Italy, Male, Molecular Sequence Data, Mutation ,genetics, Pedigree, Phenotype, Phosphoproteins ,chemistry, Polymorphism ,Single-Stranded Conformational, Protein Structure ,Tertiary, Proteins ,chemistry/genetics/metabolism, Sequence Alignment, Syndrome, X Chromosome ,Binding Sites ,Proteins ,Cell Biology ,medicine.disease ,Phosphoproteins ,Molecular biology ,Protein Structure, Tertiary ,Amino Acid Substitution ,Mutation ,biology.protein ,Sequence Alignment ,Tertiary - Abstract
Aarskog–Scott Syndrome (AAS) is an X-linked disorder characterised by short stature and multiple facial, limb and genital abnormalities. A gene, FGD1, altered in a patient with AAS phenotype, has been identified and found to encode a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac GEF). However, since this original report on identification of a mutated FGD1 gene in an AAS patient, no additional mutations in the FGD1 gene have been described. We analysed 13 independent patients with clinical diagnosis of AAS. One patient presented a mutation that results in a nucleotide change in exon 10 of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The mutation was found to segregate with the AAS phenotype in affected males and carrier females in the family of this patient. Interestingly, Arg-610 is located within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it corresponds to a highly conserved residue which has been involved in InsP binding in PH domains of other proteins. The same residue is often mutated in the Bruton’s tyrosine kinase (Btk) gene in patients with an X-linked agammaglobulinemia. The Arg610Gln mutation represents the first case of a mutation in the PH domain of the FGD1 gene and additional evidence that mutations in PH domains can be associated to human diseases.
- Published
- 2000