Detection of G338R FGFR2 mutation in a Vietnamese patient with Crouzon syndrome

Abstract

Crouzon syndrome is a rare autosomal dominant genetic disorder, which causes the premature fusion of the cranial suture. Fibroblast growth factor receptor 2 (FGFR2) mutations are well-known causatives of Crouzon syndrome. The current study aimed to assess the FGFR2 gene associated with Crouzon syndrome in a Vietnamese family of three generations and to characterize their associated clinical features. The family included in the present study underwent complete clinical examination. A patient was clinically examined and presented with typical features of Crouzon syndrome including craniosynostosis, shallow orbits, ocular proptosis and midface hypoplasia. However the patient had normal hands and feet, a normal hearing ability and normal intelligence. Genomic DNA collected from all family members (except from a 16 week-old-foetus) and 200 unrelated control subjects from the same population was extracted from leukocytes obtained from peripheral blood samples. Genomic DNA was extracted from the 16-week-old foetus via the amniotic fluid of the mother. All coding sequences of FGFR2 were amplified via polymerase chain reaction and directly sequenced. A heterozygous FGFR2 missense mutation (c.1012G>C, p.G338R) in exon 10 was identified in the patient with Crouzon but not in other family members, the 16 week-old-foetus or the controls. This mutation was therefore determined to be the causative agent of Crouzon syndrome. In addition, a novel heterozygous silent mutation (c.1164C>T, p.I388I) in exon 11 of the FGFR2 gene was identified in the patient with Crouzon, his mother and the 16-week-old fetus, but not in other family members. The mutation in exon 10 of FGRF2 was confirmed via restriction-enzyme digestion. The gain of the BsoBI site confirmed the FGFR2 mutation in exon 10 of the patient with Crouzon. This molecular finding may provide useful information to aid clinicians in the diagnosis of Crouzon syndrome and may also aid early prenatal diagnoses.

Inherited FGFR2 mutation in a Chinese patient with Crouzon syndrome and luxation of bulbus oculi provoked by trauma: a case report

“…In conclusion, we identified a mutation in FGFR2 that caused CS [11, 12]. Edema of the periorbital tissue is observed in the event of blunt injuries to the forehead and periorbital area.…”

Perceptive Anamnesis of Syndromic Craniosynostosis with Case Series of Crouzon Syndrome

“…Synostosis can be suspected during the antenatal stage via ultrasound scan or otherwise begins during the first year of life or might be evident at birth. [3][4][5][6][7][8] Genetic Update: Syndromic craniosynostosis comprises 15-30% of the total, and specific single-gene mutations or chromosome abnormalities could be identified in 10 Other manifestations include elliptical-shaped head, with dolicofacial growth pattern, concave facial profile, and long face with proptosis.…”

“…19 Furthermore, the successful diagnosis of CS during pregnancy may occur via chorionic villus biopsy using polymerase chain reaction (PCR) by targeting FGFR2, a known mutation found within the pregnant mother. 12,6 Prenatal real-time ultrasonographic diagnosis of exophthalmos is possible at the 35 th week of gestation in a fetus affected with crouzon syndrome. 6,14 It is essential to be well informed of the late-onset pansynostosis of CS, which occurs occasionally; because the slight distortion of the skull shape may disguise the presence of raised ICP.…”

“…12,6 Prenatal real-time ultrasonographic diagnosis of exophthalmos is possible at the 35 th week of gestation in a fetus affected with crouzon syndrome. 6,14 It is essential to be well informed of the late-onset pansynostosis of CS, which occurs occasionally; because the slight distortion of the skull shape may disguise the presence of raised ICP. 11,13 Matter of Contention: Copper Beaten Skull: Copper beaten skull, also known as beaten silver skull or beaten brass skull, refers to the prominence of convolutional markings (gyral impressions on the inner table of the skull) seen throughout the skull vault.…”

Crouzon syndrome complicated with binocular strabismus and extraocular muscle fibrosis: a case report

“…The disease is generally inherited in an autosomal dominant manner [ 2 ] and has an incidence of 1/60,000 to 1.65/100,000 [ 3 ]. The mutant gene in most patients is located on the fibroblast growth factor receptor 2 ( FGFR2 ) gene fragment on chromosome 10q25-q26 [ 4 – 6 ]. Common eye damage resulting from the premature closure of cranial sutures due to Crouzon syndrome is attributable to increased intracranial pressure, nerve traction, and/or narrowing of the optic foramen, all of which can contribute to optic nerve atrophy and even blindness [ 7 ].…”