Zi-Li Li1, Xue Chen2, Wen-Juan Zhuang1, Wei Zhao3, Ya-Ni Liu1, Fang-Xia Zhang1, Ruo-Shui Ha4, Jin-Hua Wu4, Chen Zhao2, Xun-Lun Sheng1. 1. 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. 2. Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing 210029, Jiangsu Province, China. 3. Central Laboratory of Ningxia Medical University, Yinchuan 750000, Ningxia Hui Autonomous Region, China. 4. Department of Radiology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan 750000, Ningxia Hui Autonomous Region, China.
Abstract
AIM: 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 the FGFR2 gene 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, FGFR2 p.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. CONCLUSION: 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.
AIM: 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 the FGFR2 gene 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, FGFR2 p.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. CONCLUSION: 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.
Authors: Andrew O M Wilkie; Elena G Bochukova; Ruth M S Hansen; Indira B Taylor; Sahan V Rannan-Eliya; Jo C Byren; Steven A Wall; Lina Ramos; Margarida Venâncio; Jane A Hurst; Anthony W O'rourke; Louise J Williams; Anneke Seller; Tracy Lester Journal: Am J Med Genet A Date: 2007-08-15 Impact factor: 2.802
Authors: Pablo Lapunzina; Alejandra Fernández; Juan M Sánchez Romero; Alicia Delicado; Miguel Sáenz de Pipaon; Isidora López Pajares; Jesús Molano Journal: Birth Defects Res A Clin Mol Teratol Date: 2005-01
Authors: Anh Lan Thi Luong; Thuong Thi Ho; Ha Hoang; Trung Quang Nguyen; Tu Cam Ho; Phan Duc Tran; Thuy Thi Hoang; Nam Trung Nguyen; Hoang Ha Chu Journal: Biomed Rep Date: 2019-01-03