Table 1

Selected genes causal to skeletal diseases and disorders

OMIM #

Gene name

Gene symbol

Diseases and disorders


114290

Sry-related HMG-box gene 9

SOX9

Acampomelic campomelic dysplasia

Campomelic dysplasia

Campomelic dysplasia with autosomal sex reversal

120110

Collagen, type X alpha-1

COL10A1

Metaphyseal chondrodysplasia, Schmid type

Spondylometaphyseal dysplasia, Japanese type

120140

Collagen, type II alpha-1

COL2A1

Achondrogenesis, type II

Achondrogenesis-hypochondrogenesis, type II

Hypochondrogenesis

Kniest dysplasia

Osteoarthritis with mild chondrodysplasia

Spondyloepimetaphyseal dysplasia, Strudwick type

Spondyloepiphyseal dysplasia, various types

Spondylometaphyseal dysplasia, congenital type

Spondyloperipheral dysplasia

Stickler syndrome, type I

Wagner syndrome

120150

Collagen, type I alpha-1

COL1A1

Ehlers–Danlos syndrome, types I and VIIA

Osteogenesis imperfecta, types I, II, III, and IV

120160

Collagen, type I alpha-2

COL1A2

Ehlers–Danlos syndrome, type VII-B

Osteogenesis imperfecta, types II, III, and IV

Osteogenesis imperfecta/Ehlers–Danlos crossover syndrome

Marfan syndrome, atypical

120180

Collagen, type III alpha-1

COL3A1

Arterial and aortic aneurysms

Ehlers–Danlos syndrome, types III and IV

120190

Collagen, type V alpha-2

COL5A2

Ehlers–Danlos syndrome, types I and II

120215

Collagen, type V alpha-1

COL5A1

Ehlers–Danlos syndrome, types I, II, and mixed type

120260

Collagen, type IX alpha-2

COL9A2

Epiphyseal dysplasia, multiple, type 2

Intervertebral disc disease

120270

Collagen, type IX alpha-3

COL9A3

Epiphyseal dysplasia, multiple, type 3

Epiphyseal dysplasia, multiple, with myopathy

120280

Collagen, type XI alpha-1

COL11A1

Stickler syndrome, type II

Marshall syndrome

120290

Collagen, type XI alpha-2

COL11A2

Sensorineural deafness, autosomal dominant nonsyndromic

Otospondylomegaepiphyseal dysplasia

Stickler syndrome, type III

Weissenbacher–Zweymuller syndrome

120360

Matrix metalloproteinase 2

MMP2

Osteolysis, idiopathic, Saudi type

121050

Fibrillin 2

FBN2

Contractural arachnodactyly, congenital

123101

Muscle segment homeobox 2

MSX2

Craniosynostosis, Boston-type

Parietal foramina 1

125505

Deoxyribonuclease I

DNASE1

Systemic lupus erythematosus susceptibility

133700

Exostosin 1

EXT1

Exostoses, multiple, type 1

Chondrosarcoma

133701

Exostosin 2

EXT2

Exostoses, multiple, type II

134797

Fibrillin 1

FBN1

Marfan syndrome, various types

Ectopia lentis, familial

Marfanoid skeletal syndrome

Mass syndrome

Shprintzen-Goldberg syndrome

134934

Fibroblast growth factor receptor 3

FGFR3

Achondroplasia

Crouzon syndrome with acanthosis nigricans

Hypochondroplasia

Muenke syndrome

Multiple myeloma

Saddan dysplasia

Thanatophoric dysplasia, types I and II

136350

Fibroblast growth factor receptor 1

FGFR1

Pfeiffer syndrome

139250

Growth hormone 1

GH1

Growth hormone deficiency

Isolated growth hormone deficiency, type I

Kowarski syndrome

139320

Guanine nucleotide-binding protein,

GNAS1

Mccune–Albright syndrome

alpha-stimulating activity polypeptide 1

Albright hereditary osteodystrophy

Pituitary adenoma, ACTH-secreting

142461

Heparan sulfate proteoglycan

HSPG2

Schwartz–Jampel syndrome, type 1

of basement membrane, perlecan

Dyssegmental dysplasia, Silverman–Handmaker type

142958

Homeobox A11

HOXA11

Radioulnar synostosis with amegakaryocytic thrombocytopenia

147620

Interleukin 6

IL6

Interleukin 6 polymorphism associated with systemic onset

juvenile rheumatoid arthritis

154870

Matrix gamma-carboxyglutamic

MGP

Keutel syndrome

acid protein

156845

Microphthalmia-associated

MITF

Waardenburg syndrome, type IIA

transcription factor

Tietz albinism–deafness syndrome

157660

Mitochondrial RNA-processing

RMRP

Cartilage–hair hypoplasia

endoribonuclease (RNA component of)

168450

Parathyroid hormone

PTH

Hypoparathyroidism

168468

Parathyroid hormone receptor 1

PTHR1

Metaphyseal chondrodysplasia, Murk Jansen type

Chondrodysplasia, Blomstrand type

176943

Fibroblast growth factor receptor 2

FGFR2

Apert syndrome

Beare–Stevenson cutis gyrata syndrome

Craniosynostosis, nonsyndromic unicoronal

Crouzon syndrome

Jackson–Weiss syndrome

Pfeiffer syndrome

Saethre–Chotzen syndrome

190180

Transforming growth factor, beta-1

TGFB1

Camurati–Engelmann disease

193500

Paired box gene 3

PAX3

Waardenburg syndrome, types I, II, and III

Waardenburg syndrome with meningomyelocele

Rhabdomyosarcoma, alveolar

Craniofacial–deafness–hand syndrome

203500

Homogentisate 1,2-dioxygenase

HGD

Alkaptonuria

217000

Complement component 2

C2

Complement component 2 deficiency

222600

Solute carrier family 26, member 2

SLC26A2

Achondrogenesis, type IB

Atelosteogenesis, type II

Diastrophic dysplasia

249100

Familial Mediterranean fever gene

MEFV

Familial Mediterranean fever

277900

ATPase, Cu(2+)-transporting,

ATP7B

Wilson Disease

beta polypeptide

300202

Sedlin

SEDL

Spondyloepiphyseal dysplasia, late

300300

Bruton agammaglobulinemia

BTK

Agammaglobulinemia, X-linked associated with

tyrosine kinase

septic arthritis

308000

Hypoxanthine guanine

HPRT1

Gout, HPRT-related

phosphoribosyltransferase 1

Lesch–Nyhan syndrome

311850

Phosphoribosylpyrophosphate

PRPS1

Gout, PRPS-related

synthetase I

312865

Short stature homeobox

SHOX

Short stature, idiopathic

Leri–Weill dyschondrosteosis

Langer mesomelic dysplasia

600211

Runt-related transcription factor 2

RUNX2

Cleidocranial dysplasia

600310

Cartilage oligomeric matrix protein

COMP

Epiphyseal dysplasia

Pseudoachondroaplasia

600725

Sonic hedgehog

SHH

Holoprosencephaly 3

600726

Indian hedgehog

IHH

Brachydactyly type A1

600856

Cyclin-dependent kinase inhibitor 1C

CDKN1C

Beckwith–Wiedemann syndrome

600946

Growth hormone receptor

GHR

Laron syndrome

Short stature, autosomal dominantand idiopathic

601105

Cathepsin K

CTSK

Pycnodysostosis

601146

Growth/differentiation factor 5

GDF5

Acromesomelic dysplasia, Hunter–Thompson type

Brachydactyly, type C

Chondrodysplasia, Grebe type

601199

Calcium-sensing receptor

CASR

Hypercalciuric hypercalcemia

Hypercalciuric hypocalcemia

Hyperparathyroidism

Hypocalcemia

Hypocalciuric hypercalcemia

Hypoparathyroidism, various types

601309

Patched

PTCH

Basal cell nevus syndrome

Basal cell carcinoma, sporadic

601769

Vitamin D receptor

VDR

Vitamin D-resistant rickets, type II

602109

Matrilin 3

MATN3

Multiple epiphyseal dysplasia

602337

Receptor tyrosine kinase-like

ROR2

Brachydactyly, type B1

Orphan receptor 2

Robinow syndrome, autosomal recessive

602365

Cathepsin C

CTSC

Papillon–Lefevre syndrome

Haim–Munk syndrome

602727

Chloride channel 7

CLCN7

Osteopetrosis, Autosomal Recessive, Infantile Malignant

602991

Noggin

NOG

Symphalangism, proximal

Multiple synostoses syndrome 1

603400

Wnt1-inducible signaling

WISP3

Arthropathy, progressive pseudorheumatoid of childhood

pathway protein 3

603499

Tumor necrosis factor receptor

TNFRSF11A

Expansile osteolysis, familial

superfamily, 11A

Paget disease of bone 2

604142

Tyro protein tyrosine

TYROBP

Polycystic lipomembranous osteodysplasia with sclerosing

kinase-binding protein

leukoencephalopathy

604283

Proteoglycan 4

PRG4

Camptodactyly–arthropathy–coxa vara–pericarditis syndrome

604592

T cell immune regulator 1

TCIRG1

Osteopetrosis, autosomal recessive

604831

Ellis–Van Creveld syndrome gene

EVC

Ellis-Van Creveld syndrome

Weyers acrodental dysostosis

605145

Ank

ANKH

Craniometaphyseal dysplasia, autosomal dominant

605380

Fibroblast growth factor 23

FGF23

Hypophosphatemic rickets, autosomal dominant

605420

Aristaless-like 4,

ALX4

Parietal foramina 2

605740

Sclerostin

SOST

Sclerosteosis


Mutations in a number of genes have been shown to cause congenital skeletal disorders, often with defects in cartilage formation as the primary basis. Others predispose the individual towards skeletal diseases such as arthritis. The completed sequence of the human genome opens the door for rapid identification of additional genetic mutations associated with human diseases and disorders. Functional genomics and the characterization of molecular mechanisms bridging genotypes to phenotypes are our challenges to realize solutions for the prevention, detection, diagnosis and therapy of these diseases and disorders. Data extracted from Online Mendelian Inheritance in Man (OMIM) [113].

Shum and Nuckolls Arthritis Res 2002 4:94-106   doi:10.1186/ar396