FGFR1 and FGFR2 Mutations in Pfeiffer Syndrome : Journal of Craniofacial Surgery (original) (raw)

Original Articles

Chokdeemboon, Chayanin BSc*†; Mahatumarat, Charan MD‡; Rojvachiranonda, Nond MD‡; Tongkobpetch, Siraprapa MSc†§; Suphapeetiporn, Kanya MD, PhD*†§; Shotelersuk, Vorasuk MD†§

From the *Interdepartment of Biomedical Sciences, Faculty of Graduate School, †Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University; ‡Department of Surgery, Faculty of Medicine, and §Clinical Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand.

Received February 1, 2012.

Accepted for publication June 6, 2012.

Address correspondence and reprint requests to Kanya Suphapeetiporn, MD, PhD, Department of Pediatrics, Sor Kor Building 11th floor, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; E-mail: [email protected]

This study was supported by Chulalongkorn University Dutsadi Phiphat Scholarship, Chulalongkorn University Graduate Scholarship to commemorate the 72th Anniversary of His Majesty the King Bhumibol Adulyadej, the Thailand Research Fund, the National Science and Technology Development Agency, the National Research University Project of CHE, and the Ratchadapiseksomphot Endowment Fund (HR1163A).

The authors report no conflicts of interest.

Abstract

Pfeiffer syndrome (PS) (MIM 101600) is one of the most common syndromic forms of craniosynostosis. It is characterized by craniosysnostosis, midface hypoplasia, broad and medially deviated thumbs, and great toes with partial syndactyly of the digits. Here, we described clinical and genetic features of 12 unrelated Thai individuals with PS. All 12 patients were sporadic, and advanced paternal age was found in 50% of the cases. Polymerase chain reaction sequencing of FGFR1 exon 5 and FGFR2 exons 8, 10, 15, 16, and 17 was performed in all PS patients and revealed 9 recurrent mutations in all patients. Most of the mutations clustered in exons 8 and 10 (9/12) accounting for 75% of PS cases. The most frequently detected mutation, p.S351C, was associated with the severe form of PS in the Thai population. Less frequent mutations in exons 16 (p.K641R) and 17 (p.G663E) were also identified. In addition, the p.P252R mutation in FGFR1 was detected in 1 PS patient with unilateral coronal craniosynostosis expanding the phenotypic spectrum of PS with this particular mutation. Knowing the mutation spectrum of the responsible genes could lead to the most effective strategy in identifying mutations causing Pfeiffer syndrome in the Thai population.