Q289P mutation in FGFR2 gene causes Saethre-Chotzen syndrome: some considerations about familial heterogeneity.
OBJECTIVE
To describe the first report on a three-generation family presenting typical features of Saethre-Chotzen syndrome, in which the Q289P mutation in the FGFR2 gene was detected.


METHODS
Dysmorphological evaluation was performed by a clinical geneticist. Direct sequencing of the polymerase chain reaction-amplified coding region of TWIST and screening for the P250R mutation in the FGFR3 gene were performed. Exons IIIa and IIIc of FGFR2 were sequenced also. The mutation was confirmed by both restriction-enzyme digestion and allelic-specific polymerase chain reaction.


RESULTS
Neither TWIST gene analysis nor analysis of the P250R mutation on gene FGFR3 showed mutation within the coding sequence. A nucleotide change from CAG to CCG in exon IIIa of the FGFR2 gene that caused a Q289P mutation was detected, although exon IIIc in the propositus was normal. These same results were detected in his mother, but no other members of the kindred presented clinical features consistent with Saethre-Chotzen syndrome.


CONCLUSIONS
This mutation was previously reported in individuals with Crouzon and Jackson-Weiss syndromes. The FGFR2 mutation in the family with Saethre-Chotzen syndrome herein reported reinforces the idea of an interaction among TWIST and FGFR genes during development. Absence of the Q289P mutation in some affected individuals in this family is discussed.
Freitas
Erika Cristina Lopes Burrone de
EC
Ciências Médicas, Departamento de Genética Médica, Universidade Estadual de Campinas, 13083-970 Campinas, São Paulo, Brazil.
Nascimento
Sandra Regina Dantas
SR
de Mello
Maricilda Palandi
MP
Gil-da-Silva-Lopes
Vera Lúcia
VL
D000168:Acrocephalosyndactylia / Q000235:genetics*; D000465:Algorithms; D003398:Craniosynostoses / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000235:genetics
D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2