FGFR2 mutations and associated clinical observations in two Chinese patients with Crouzon syndrome

Abstract

The aim of the present study was to identify mutations in the fibroblast growth factor receptor 2 (FGFR2) gene in patients with Crouzon syndrome and characterize the associated clinical features. A total of two Chinese patients diagnosed with Crouzon syndrome underwent complete examinations, including best‑corrected visual acuity, slit‑lamp, examination, fundus examination, optical coherence tomography and computed tomography of the skull. Genomic DNA was extracted from peripheral blood samples collected from the patients, as well as their family members and 200 unrelated control subjects from the same population. Exons 8 and 10 in the FGFR2 gene were amplified by polymerase chain reaction and directly sequenced. Patient #1 had a heterozygous missense mutation (c.1025G>A, p.C342Y) in exon 10 of FGFR2. Patient #2 had a heterozygous mutation (c.1084+1 G>T; IVS10+1G>T) in intron 10. The mutations were not present in any of the unaffected family members or unrelated control subjects. These findings expand the mutation spectrum of FGFR2, and are valuable for genetic counseling in addition to prenatal diagnosis in patients with Crouzon syndrome.

Figure 1.

Clinical manifestations of patient #1. (A and B) The patient presented with ocular proptosis (white arrows), extropia, midface hypoplasia (black asterisk), craniosynostosis (white arrowhead), and a curved, beak-like nose (black arrowhead). An approximately 2 mm gap was observed when she attempted to close her eyelids. (C and D) The corneas of both eyes were transparent with normal size, and the lenses are clear and normally postioned. (E and F) Fundus examination showed normal retina in both eyes. (G) A CT scan reveals shallow orbits and exotropia in both eyes (white asterisks).

Figure 2.

Clinical manifestations of patient #2. (A) The patient presented with midface hypoplasia (black asterisk). (B) Clinically normal hands. (C) Radiography revealed no obvious carpal fusions in this patient. (D and E) The cornea and lenses were normal. (F) CT scan revealed shallow orbits (white asterisks). (G and H) OCT examination revealed normal retina in both eyes.

Figure 3.

Mutational screening results of the patients. (A) A heterozygous missense mutation (c.1025G>A; p.C342Y) in exon 10 of the FGFR2 gene was identified in patient #1. (B) A heterozygous mutation (IVS10+1 G>T; c.1084+1 G>T) in intron 10 of the FGFR2 gene was identified in patient #2. Yellow boxes denote exon regions. Pink boxes denote intron regions.