Mr. Passosbueno et al., DESCRIPTION OF A NEW MUTATION AND CHARACTERIZATION OF FGFR1, FGFR2, AND FGFR3 MUTATIONS AMONG BRAZILIAN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSES, American journal of medical genetics, 78(3), 1998, pp. 237-241
Dominant mutations in three fibroblast growth factor receptor genes (F
GFRs1-3) cause Crouzon, Jackson-Weiss, Pfeiffer, and Apert syndromes.
In the present study, 50 Brazilian patients with these four syndromes
(27 Apert, 17 Crouzon, 5 Pfeiffer, and 1 Jackson-Weiss patients) were
screened for mutations in the FGFR1-3 genes. Except for one, all the A
pert patients had either S252W (n = 16) or P253R (n = 10) mutations. T
he remaining Apert case is atypical with a mutation altering the splic
e site of FGFR2 exon IIIc. The Pfeiffer patients had mutations in one
of the FGFR genes: three in FGFR2, one in FGFR1, and one in FGFR3. In
contrast, only 8 of the 17 Crouzon patients studied had a mutation in
either FGFR2 (n = 7) or FGFR3 locus (n = 1). Mutations in the FGFR2 lo
cus account for most (93%) of our syndromic craniosynostotic cases, wh
ereas 5% had mutations in the FGFR3 locus and only 2% had mutations in
the FGFR1 gene. Except for one, all the other mutations were reported
previously in craniosynostotic patients from other populations. Inter
estingly, the mutation C278F, previously described in Crouzon and Pfei
ffer cases, was here identified in a familial case with Jackson-Weiss.
Also, unexpectedly, a common mutation altering the splice site of the
FGFR2 exon IIIc was found in one Apert and two Pfeiffer patients. In
addition, we identified a new mutation (A337P) in the FGFR2 exon IIIc
associated with Crouzon phenotype. (C) 1998 Wiley-Liss, Inc.