PMID- 10574673
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20180607
IS  - 1055-6656 (Print)
IS  - 1055-6656 (Linking)
VI  - 36
IP  - 6
DP  - 1999 Nov
TI  - A novel FGFR2 gene mutation in Crouzon syndrome associated with apparent
      nonpenetrance.
PG  - 533-41
AB  - OBJECTIVE: To determine whether specific mutations within the fibroblast growth
      factor receptor 2 (FGFR2) gene that are associated with Crouzon syndrome can be
      present in an individual who had been assumed to be "clinically normal." METHODS:
      Most mutations responsible for Crouzon syndrome occur in exons IIIa (U) or IIIc
      (B) of the FGFR2 gene, which facilitates allelotyping using polymerase chain
      reaction (PCR)-mediated mutation analysis. Once a specific mutation was
      identified in the index case, remaining affected family members and "clinically
      normal" first-degree relatives were analyzed in order to correlate genotype with 
      phenotype. RESULTS: A novel missense mutation--a G to T transversion--involving
      the first base of codon 362 was identified in all Crouzon syndrome-affected
      family members and in one "clinically normal"-appearing parent following DNA
      sequencing of exon B of the FGFR2 gene and specific BstNI restriction fragment
      length polymorphism. Pattern profile analysis demonstrated a consistent
      collection of abnormal cephalometric measurements in the Crouzon-affected family 
      members and, to a lesser degree, in the "clinically normal" parent. CONCLUSION:
      We have identified a novel missense mutation in the FGFR2 gene that predicts an
      Ala362Ser substitution shared by all family members affected by Crouzon syndrome 
      and by a "clinically normal"-appearing father. These data support nonpenetrance
      of Crouzon syndrome when the diagnosis is based on clear clinical findings. Only 
      through cephalometry was there an indication of minimal expression of Crouzon
      syndrome in the "clinically normal"-appearing father.
FAU - Everett, E T
AU  - Everett ET
AD  - Department of Oral Facial Development, Indiana University School of Dentistry,
      Indianapolis 46202, USA.
FAU - Britto, D A
AU  - Britto DA
FAU - Ward, R E
AU  - Ward RE
FAU - Hartsfield, J K Jr
AU  - Hartsfield JK Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cleft Palate Craniofac J
JT  - The Cleft palate-craniofacial journal : official publication of the American
      Cleft Palate-Craniofacial Association
JID - 9102566
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - EC 2.7.10.1 (FGFR2 protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
SB  - IM
MH  - Cephalometry
MH  - Craniofacial Dysostosis/diagnostic imaging/*genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Head/diagnostic imaging
MH  - Humans
MH  - Male
MH  - Mutation, Missense
MH  - Pedigree
MH  - *Penetrance
MH  - Polymerase Chain Reaction
MH  - Radiography
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Receptor, Fibroblast Growth Factor, Type 2
MH  - Receptors, Fibroblast Growth Factor/*genetics
EDAT- 1999/11/26 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/11/26 09:00
PHST- 1999/11/26 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/11/26 09:00 [entrez]
AID - 10.1597/1545-1569_1999_036_0533_anfgmi_2.3.co_2 [doi]
PST - ppublish
SO  - Cleft Palate Craniofac J. 1999 Nov;36(6):533-41. doi:
      10.1597/1545-1569_1999_036_0533_anfgmi_2.3.co_2.