TY - JOUR
T1 - Mutational screening of FGFR1, CER1, and CDON in a large cohort of trigonocephalic patients
AU - Jehee, Fernanda Sarquis
AU - Alonso, Luis G.
AU - Cavalcanti, Denise P.
AU - Kim, Chong
AU - Wall, Steven A.
AU - Mulliken, John B.
AU - Sun, Miao
AU - Jabs, Ethylin Wang
AU - Boyadjiev, Simeon A.
AU - Wilkie, Andrew O M
AU - Passos-Bueno, Maria Rita
PY - 2006/3
Y1 - 2006/3
N2 - 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. Design: Using single-strand conformational polymorphisms (SSCFs), 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. Patients: 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: FGFB1 (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.
AB - 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. Design: Using single-strand conformational polymorphisms (SSCFs), 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. Patients: 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: FGFB1 (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.
KW - CDON
KW - CER1
KW - Craniosynostosis
KW - FGFR1
KW - Metopic suture
KW - Trigonocephaly
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U2 - 10.1597/04-206.1
DO - 10.1597/04-206.1
M3 - Article
C2 - 16526918
AN - SCOPUS:33644996922
SN - 1055-6656
VL - 43
SP - 148
EP - 151
JO - Cleft Palate-Craniofacial Journal
JF - Cleft Palate-Craniofacial Journal
IS - 2
ER -