FGFR2mutation in a Chinese family with unusual Crouzon syndrome.
OBJECTIVE
To describe the clinical characteristics with genetic lesions in a Chinese family with Crouzon syndrome.


METHODS
All five patients from this family were included and received comprehensive ophthalmic and systemic examinations. Direct sequencing of theFGFR2gene was employed for mutation identification. Crystal structure analysis was applied to analyze the structural changes associated with the substitution.


RESULTS
All patients presented typical Crouzon features, including short stature, craniosynostosis, mandibular prognathism, shallow orbits with proptosis, and exotropia. Intrafamilial phenotypic diversities were observed. Atrophic optic nerves were exclusively detected in the proband and her son. Cranial magnetic resonance imaging (MRI) implied a cystic lesion in her sellar and third ventricular regions. A missense mutation,FGFR2p.Cys342Trp, was found as disease causative. This substitution would generate conformational changes in the extracellular Ig-III domain of the FGFR-2 protein, thus altering its physical and biological properties.


CONCLUSIONS
We describe the clinical presentations and genotypic lesions in a Chinese family with Crouzon syndrome. The intrafamilial phenotypic varieties in this family suggest that other genetic modifiers may also play a role in the pathogenesis of Crouzon syndrome.
Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region (First Affiliated Hospital of Northwest University for Nationalities), Yinchuan 750001, Ningxia Hui Autonomous Region, China.
Zi-Li
ZL
Li
Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing 210029, Jiangsu Province, China.
Xue
X
Chen
Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region (First Affiliated Hospital of Northwest University for Nationalities), Yinchuan 750001, Ningxia Hui Autonomous Region, China.
Wen-Juan
WJ
Zhuang
Central Laboratory of Ningxia Medical University, Yinchuan 750000, Ningxia Hui Autonomous Region, China.
Wei
W
Zhao
Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region (First Affiliated Hospital of Northwest University for Nationalities), Yinchuan 750001, Ningxia Hui Autonomous Region, China.
Ya-Ni
YN
Liu
Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region (First Affiliated Hospital of Northwest University for Nationalities), Yinchuan 750001, Ningxia Hui Autonomous Region, China.
Fang-Xia
FX
Zhang
Department of Radiology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan 750000, Ningxia Hui Autonomous Region, China.
Ruo-Shui
RS
Ha
Department of Radiology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan 750000, Ningxia Hui Autonomous Region, China.
Jin-Hua
JH
Wu
Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing 210029, Jiangsu Province, China.
Chen
C
Zhao
Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region (First Affiliated Hospital of Northwest University for Nationalities), Yinchuan 750001, Ningxia Hui Autonomous Region, China.
Xun-Lun
XL
Sheng
Crouzon syndrome; FGFR2 mutation; familial cases; phenotypic diversity