Mutation analysis of FGFR1-3 in 11 Japanese patients with syndromic craniosynostoses.
Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed FGFR1-3 genes in four patients with Crouzon syndrome (CS), four patients with Pfeiffer syndrome type 2 (PS-2), one patient with Jackson-Weiss syndrome (JWS), and two patients (sisters) with Muenke syndrome (MS). FGFR2 and FGFR3 mutations were identified in 10 of the 11 patients. Notably, we found a novel FGFR2 p.Asn549Thr mutation in a patient with CS, and a novel FGFR2 p.Ser347Cys mutation in a patient with JWS (thus, this patient was turned out to have an FGFR2-related PS-variant). We also identified an FGFR2 p.Ser252Leu mutation in a phenotypically normal father of a daughter with CS, and an FGFR3 p.Pro250Arg mutation in a mildly macrocephalic father of sisters with MS. These findings, together with previous data, imply that the same FGFR2 mutations can be associated with a wide range of phenotypes including clinically different forms of syndromic craniosynostosis and apparently normal phenotype, depending on other (epi)genetic and environmental factors. Thus, genetic studies are recommended not only for obviously affected individuals but also for family members with apparently normal phenotype or non-specific subtle abnormal phenotype, to allow for pertinent genetic counseling. © 2016 Wiley Periodicals, Inc.
Department of Regional Neonatal-Perinatal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Akira
A
Ohishi
Department of Radiology, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
Gen
G
Nishimura
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Fumiko
F
Kato
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hiroyuki
H
Ono
Department of Pediatrics, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
Kaori
K
Maruwaka
Department of Neonatology, Tokyo Women's Medical University, Tokyo, Japan.
Mako
M
Ago
Department of Pediatrics, Dokkyo Medical University School of Medicine, Tochigi, Japan.
Hiroshi
H
Suzumura
Department of Neonatology, Seirei-Hamamatsu General Hospital, Hamamatsu, Japan.
Etsuko
E
Hirose
Department of Plastic, Reconstructive and Anesthetic Surgery, Chiba University School of Medicine, Chiba, Japan.
Yuki
Y
Uchida
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Maki
M
Fukami
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Tsutomu
T
Ogata
D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D003952:Diagnostic Imaging / Q000379:methods; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D009154:Mutation; D010641:Phenotype; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D013577:Syndrome
D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3
FGFR2; FGFR3; mutation; syndromic craniosynostosis