Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis.
Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome.
Apert syndrome is a genetic disorder known as acrocephalopolysyndactyly type 1 caused by mutations in the fibroblast growth factor receptor 2 and characterized by coronal craniosynostosis, symmetric bone and skin syndactyly of hands and feet, and craniofacial dysmorphic features.
Recently, a unique Pro250Arg point mutation in fibroblast growth factor receptor 3 (FGFR3) was reported in 61 individuals with coronal craniosynostosis from 20 unrelated families [Muenke et al.(1997): Am J Hum Genet 60:555-564].
A recurrent point mutation in the fibroblast growth factor receptor 3 gene that converts proline 250 into arginine has been reported recently in cases of apparently nonsyndromic coronal craniosynostosis.
We conclude that although both cranial and long bone development is variably affected by the murine Fgfr3(P244R) mutation, coronal craniosynostosis is not reliably reproduced.
Muenke-type craniosynostosis is defined as fibroblast growth factor receptor 3 (FGFR3)-associated coronal craniosynostosis with or without mental retardation.