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要旨:
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 TO of
the FGD1 gene (G2559 > A) substituting a Gin 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 PII
domain of the FGD1 gene and additional evidence that mutations in PH
domains can be associated to human diseases. (C) 2000 Federation of
European Biochemical Societies. Published by Elsevier Science B.V. All
rights reserved.
