FGFR1 and membrane partners
The gene on chromosome 8p12 that encodes fibroblast growth factor receptor-1 (OMIM:136350, UniProtKB:P11362), a tyrosine-protein kinase which acts as cell-surface receptor for fibroblast growth factors and plays an essential role in regulating embryonic development, cell proliferation, differentiation and migration. It is required for normal mesoderm patterning and correct axial organization during embryonic development, skeleton formation and development of the gonadotropin-releasing hormone neuronal system.
Molecular pathology Defects of FGFR1 cause:
• Encephalocraniocutaneous lipomatosis A neurocutaneous disorder (OMIM:613001) characterised by ocular anomalies, skin lesions, and CNS anomalies.
Clinical findings Well-demarcated hairless fatty nevus on scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital defects of meninges, variably accompanied by seizures, spasticity, and mental retardation.
• Hartsfield syndrome An autosomal dominant disorder (OMIM:615465) characterised by a triad of holoprosencephaly, ectrodactyly, and cleft/lip palate, as well as profound mental retardation, often with multiple other congenital anomalies, in particular, midline and limb field defects.
• Hypogonadotropic hypogonadism 2 with or without anosmia An autosomal dominant disorder (OMIM:147950) characterised by absent or incomplete sexual maturation by age 18, low circulating gonadotropins and testosterone and no other hypothalamic-pituitary axis defects. It may be associated with anosmia* or hyposmia due to absence or hypoplasia of olfactory bulbs and tracts, cleft palate, and sensorineural hearing loss. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons.
*In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is known as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
• Jackson-Weiss syndrome An autosomal dominant disorder (OMIM:123150) characterized by craniosynostosis, midfacial hypoplasia, and foot anomalies—broad great toes with medial deviation and tarsal-metatarsal coalescence.
• Osteoglophonic dysplasia An autosomal dominant disorder (OMIM:166250) characterized by craniosynostosis, prominent supraorbital ridge, depressed nasal bridge, rhizomelic dwarfism and nonossifying bone defects.
Osteoglophonic is an ad hoc adjective referring to hollowed out bone
• Pfeiffer syndrome An autosomal dominant disorder (OMIM:101600) characterized by craniosynostosis, broad, short and deviated thumbs and great toes, and variable syndactyly of fingers and toes.
Type 1 Mild, autosomal dominant form
Type 2 Cloverleaf skull, elbow ankylosis, early death, sporadic
Type 3 Craniosynostosis, early demise, sporadic
• Trigonocephaly 1 An autosomal dominant disorder (OMIM:190440) characterized by a triad of holoprosencephaly, ectrodactyly, and cleft/lip palate, profound mental retardation, often with multiple other congenital anomalies, in particular, midline and limb field defects.
Defects of FGFR1 also cause stem cell myeloproliferative disorder and have been linked to luminal cancer of the breast
Synonyms BFGFR, CD331, CEK, EC 18.104.22.168, FGFBR, FLG, FLT2, HBGFR, HH2, HRTFDS, KAL2, N-SAM,