Table 2.
Other monogenic bone diseases and syndromes featuring childhood-onset bone fragility and/or increased susceptibility to fractures
| Disease/syndrome | Phenotype MIM no. | Gene, inheritance | Encoded protein | Protein function |
|---|---|---|---|---|
| B3GAT3 deficiency | 245600 | B3GAT3, AR | Beta-1,3-glucuronyltransferase 3 | Glycosaminoglycans biosynthesis |
| Bruck syndrome 1 | 259450 | FKBP10, AR | 65 kDa FK506-binding protein | Collagen processing and crosslinking |
| Bruck syndrome 2 | 609220 | PLOD2, AR | Lysyl Hydroxylase 2 | Collagen processing and crosslinking |
| Cole-Carpenter dysplasia 1 | 112240 | P4HB, AD | Prolyl 4-hydroxylase subunit beta | Collagen post-translational modification |
| Cole-Carpenter dysplasia 2 | 616294 | SEC24D, AR | SEC24 homolog D, COPII coat complex component | Vesicle trafficking |
| Cutis laxa, autosomal recessive form, type 2A | 219200 | ATP6V0A2, AR | ATPase H+ transporting V0 subunit A2 | Acidification of diverse cellular components |
| Cutis laxa, autosomal recessive form, type 2B | 612940 | PYCR1, AR | Pyrroline-5-carboxylate reductase 1 | Secretory pathway |
| Ehlers-Danlos syndrome, kyphoscoliotic type, 1 | 225400 | PLOD1, AR | Lysyl hydroxylase 1 | Collagen processing and crosslinking |
| Ehlers-Danlos syndrome, kyphoscoliotic type, 2 | 614557 | FKBP14, AR | FK506-binding protein 14 | Collagen processing |
| Familial expansile osteolysis | 174810 | TNFRSF11A, AD | Tumor necrosis factor receptor superfamily member 11A | Activation of NF-kappa B and MAPK8/JNK pathways |
| Geroderma osteodysplasticum | 231070 | GORAB, AR | Golgin, RAB6 interacting | Secretory pathway |
| Gnathodiaphyseal dysplasia | 166260 | ANO5, AD | Anoctamin 5 | Control of muscle contraction and relaxation |
| Hajdu-Cheney syndrome | 102500 | NOTCH2, AD | Notch receptor 2 | Bone remodelling and homeostasis |
| Hypophosphatasia, Odontohypophosphatasia | 146300 | ALPL, AD, AR | Alkaline phosphatase, tissue-nonspecific isozyme | Skeletal mineralization |
| Metaphyseal dysplasia with maxillary hypoplasia | 156510 | RUNX2, AD | RUNX family transcription factor 2 | Osteoblast differentiation |
| Osteopetrosis | 166600, 611490 | CLCN7, AD, AR | Chloride voltage-gated channel 7 | Lysosomal function and bone resorption |
| Osteopetrosis with renal tubular acidosis | 259730 | CA2, AR | Carbonic anhydrase 2 | Bone resorption and osteoclast differentiation |
| Osteopetrosis, autosomal recessive 2 | 259710 | TNFSF11, AR | Osteoprotegerin ligand | Osteoclast differentiation and activation |
| Paget’s disease, juvenile form | 239000 | TNFRSF11B, AR | Osteoprotegerin | Osteoclastogenesis |
| Pycnodysostosis | 265800 | CTSK, AR | Cathepsin K | Bone resorption |
| Short stature, optic nerve atrophy and Pelger-Huet anomaly | 614800 | NBAS, AR | NBAS subunit Of NRZ tethering complex | Golgi-to-ER transport |
| Singleton-Merten dysplasia 1 | 182250 | IFIH1, AD | Interferon induced with helicase C domain 1 | RNA helicase |
| Singleton-Merten dysplasia 2 | 616298 | DDX58, AD | DExD/H-box helicase 58 | RNA helicase |
| Spondylo-ocular syndrome | 605882 | XYLT2, AR | Xylosyltransferase 2 | Biosynthesis of proteoglycans |
| Wiedemann-Rautenstrauch syndrome | 264090 | POLR3A, AR | RNA polymerase III subunit A | Synthesis of small RNAs |
AD, autosomal dominant; AR, autosomal recessive; MIM, Mendelian inheritance in Man. List of conditions from Mortier et al., 2019 [52]