Table 3.
Heritable Mutations in FGFs Associated with Disease in Humans (and Mice)
| Gene Name | Mutation | Associated Disease | Selected References |
|---|---|---|---|
| (a) Heritable mutations in FGFs associated with disease in humans (and other mammals) | |||
| FGF1 | |||
| FGF2 | |||
| FGF3 | Haploinsufficiency | Oto-dental syndrome | 479,514–517 |
| Missense/frameshift mutation | Michel aplasia (inner ear agenesis, microtia, and microdontia), LAMM syndrome (labyrinthine aplasia, microtia, and microdontia) | ||
| FGF4 | Retroviral overexpression | Chondrodysplasia (dogs) | 16 |
| FGF5 | Deletion mutation | Angora mutation (mice) | 18,518–521 |
| Missense/splice-site mutation | Coat variability (pure bred dogs) | ||
| Missense/insertion/deletion mutation | Long-hair (cats) | ||
| FGF6 | |||
| FGF7 | Polymorphism | Chronic obstructive pulmonary disease risk | 522 |
| FGF8 | Nonsense mutation | Hypogonadotropic hypogonadism | 523–528 |
| Missense mutation | Cleft lip and palate, Holoprosencephaly, craniofacial defects, Hypothalamo-pituitary dysfunction, Kallman syndrome type 6 | ||
| Hypomorphic allele | Lack of hypothalamic GnRH neurons | ||
| FGF9 | Missense mutation | Multiple synostoses syndrome, Elbow knee synostosis (mice) | 469,470,529 |
| Promoter polymorphism | Sertoli cell-only syndrome | ||
| FGF10 | Nonsense mutation | Aplasia of lacrimal and salivary glands, LADD syndrome | 530–534 |
| Polymorphism | Extreme myopia | ||
| FGF11 | |||
| FGF12 | Missense mutation | Brugada syndrome (candidate gene) | 535 |
| FGF13 | Nonsense mutation | Börjeson-Forssman-Lehmann syndrome (BFLS) (candidate gene) | 536,537 |
| Position effect | X-linked congenital generalized hypertrichosis | ||
| FGF14 | Missense mutation/translocation/deletion | Spinocerebellar ataxia 27 (SCA27) | 505,538,539 |
| FGF15/19 | |||
| FGF16 | Nonsense mutation | Metacarpal 4–5 fusion | 540,541 |
| FGF17 | Missense mutation | Hypogonadotropic hypogonadism | 542 |
| FGF18 | Polymorphism | Nonsyndromic cleft lip and palate | 524 |
| FGF20 | Polymorphism | Parkinson disease risk | 40,543–545 |
| Missense mutation | Kidney agenesis (human) | ||
| FGF21 | Polymorphism | Macronutrient intake, obesity, and type-2 diabetes risk | 546–548 |
| FGF22 | |||
| FGF23 | Missense mutation | Autosomal dominant hypophosphataemic rickets, Familial hyperphosphatemic tumoral calcinosis | 242,549–555 |
| Polymorphism | Cardiac abnormality risk in Kawasaki syndrome (increased serum FGF23) | ||
| (b) Heritable mutations in FGFRs associated with disease in humans (and other mammals) | |||
| FGFR1 | Missense mutation | Pfeifer syndrome, Kallman syndrome 2, Normosmic idiopathic hypogonadotropic hypogonadism, Split hand/foot malformation, Osteoglophonic dyplasia, Harstfield syndrome | 556–566 |
| Missense or frameshift mutation | Jackson-Weiss syndrome | ||
| FGFR2 | Missense mutation | Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Pfeifer syndrome, Non syndromic craniosynostosis, Bent bone dysplasia | 567–579 |
| Deletion | Saethre-Chotzen-syndrome | ||
| FGFR3 | Missense mutation | Hypochondroplasia, Achondroplasia, Thanatophoric dysplasia, Coronal craniosynostosis, Crouzon syndrome with acanthosis nigricans, Platyspondylic lethal skeletal dysplasia, Achondroplasia with developmental delay, and acanthosis nigricans (SADDAN), Muenke syndrome, Saethre-Chotzen-syndrome, CATSHL syndrome, Mouse models for aberrant osteogenesis, Achondroplasia, Muenke syndrome | 288,574,580–611 |
| FGFR4 | Overexpression | Facioscapulohumeral muscular dystrophy | 612–614 |
| Missense mutation | Gallstone disease | ||
| Polymorphism | Bronchopulmonary dysplasia, Neonatal respiratory distress syndrome | ||
| FGFRL1 | Frameshift mutation | Craniosynostosis, Antley–Bixler-like syndrome | 615–617 |
| Deletion | Wolf-Hirshchhorn syndrome | ||