Mutation analysis of m>FGFR1-3m> in 11 Japanese patients with syndromic craniosynostoses

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• 作者：Akira Ohishi ; Gen Nishimura ; Fumiko Kato ; Hiroyuki Ono ; Kaori Maruwaka ; Mako Ago ; Hiroshi Suzumura ; Etsuko Hirose ; Yuki Uchida ; Maki Fukami and Tsutomu Ogata
• 刊名：American Journal of Medical Genetics Part A
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：173
• 期：1
• 页码：157-162
• 全文大小：529K
• ISSN：1552-4833

文摘

Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed m>FGFR1-3m> 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). m>FGFR2m> and m>FGFR3m> mutations were identified in 10 of the 11 patients. Notably, we found a novel m>FGFR2m> p.Asn549Thr mutation in a patient with CS, and a novel m>FGFR2m> p.Ser347Cys mutation in a patient with JWS (thus, this patient was turned out to have an m>FGFR2m>-related PS-variant). We also identified an m>FGFR2m> p.Ser252Leu mutation in a phenotypically normal father of a daughter with CS, and an m>FGFR3m> p.Pro250Arg mutation in a mildly macrocephalic father of sisters with MS. These findings, together with previous data, imply that the same m>FGFR2m> 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.