Mutational screening of FGFR1, CER1, and CDON in a large cohort of trigonocephalic patients.
OBJECTIVE
Screen the known craniosynostotic related gene, FGFR1 (exon 7), and two new identified potential candidates, CER1 and CDON, in patients with syndromic and nonsyndromic metopic craniosynostosis to determine if they might be causative genes.


METHODS
Using single-strand conformational polymorphisms (SSCPs), denaturing high-performance liquid chromatography, and/or direct sequencing, we analyzed a total of 81 patients for FGFR1 (exon 7), 70 for CER1, and 44 for CDON.


METHODS
Patients were ascertained in the Centro de Estudos do Genoma Humano in São Paulo, Brazil (n = 39), the Craniofacial Unit, Oxford, U.K. (n = 23), and the Johns Hopkins University, Baltimore, Maryland (n = 31). Clinical inclusion criteria included a triangular head and/or forehead, with or without a metopic ridge, and a radiographic documentation of metopic synostosis. Both syndromic and nonsyndromic patients were studied.


RESULTS
No sequence alterations were found for FGFR1 (exon 7). Different patterns of SSCP migration for CER1 compatible with the segregation of single nucleotide polymorphisms reported in the region were identified. Seventeen sequence alterations were detected in the coding region of CDON, seven of which are new, but segregation analysis in parents and homology studies did not indicate a pathological role.


CONCLUSIONS
FGFR1 (exon 7), CER1, and CDON are not related to trigonocephaly in our sample and should not be considered as causative genes for metopic synostosis. Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients.
Jehee
Fernanda Sarquis
FS
Centro de Estudos do Genoma Humano, Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 277, Sala 200 CEP 05508-900 São Paulo, SP, Brazil.
Alonso
Luis G
LG
Cavalcanti
Denise P
DP
Kim
Chong
C
Wall
Steven A
SA
Mulliken
John B
JB
Sun
Miao
M
Jabs
Ethylin Wang
EW
Boyadjiev
Simeon A
SA
Wilkie
Andrew O M
AO
Passos-Bueno
Maria Rita
MR
D015815:Cell Adhesion Molecules / Q000235:genetics*; D003398:Craniosynostoses / Q000000981:diagnostic imaging / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D029867:Xenopus Proteins
C107286:CDON protein, human; D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; C100866:cer1 protein, Xenopus; D051496:Receptor, Fibroblast Growth Factor, Type 1