Details of Disease

General Information of Disease (ID: DIS7XQSD)

• Disease Name: Osteogenesis imperfecta
• Synonyms: Vrolik disease; Fragilitas ossium; Lobstein disease; Porak and Durante disease; Lobstein's syndrome; brittle bone disease; OI; Osteopsathyrosis; Vrolik's disease; glass bone disease
• Disease Class: LD24: Skeletal anomaly
• Definition: Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity.
• Disease Hierarchy:
  DIS9SPWW: Osteochondrodysplasia
  DISYKSRF: Genetic disease
  DIS7XQSD: Osteogenesis imperfecta
• ICD Code:
  ICD-11: ICD-11: LD24.K0
  ICD-10: ICD-10: Q78.0
  ICD-9: ICD-9: 756.51
  Expand ICD-11: 'LD24.K0
  Expand ICD-10: 'Q78.0
  Expand ICD-9: 756.51
• Disease Identifiers:
  MONDO ID: MONDO_0019019
  MESH ID: D010013
  UMLS CUI: C0029434
  MedGen ID: 45246
  Orphanet ID: 666
  SNOMED CT ID: 78314001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Teriparatide	DMMC45B	Approved	Peptide	[1]

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
UX143	DM89NIB	Phase 3	Antibody	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
LRP5	TT7VMG4	Limited	Biomarker	[3]
SERPINH1	TTPSWQG	moderate	Genetic Variation	[4]
ACVR2B	TTLFRKS	Strong	Biomarker	[5]
BMP1	TT0L58T	Strong	Genetic Variation	[6]
SERPINF1	TTR59S1	Strong	Genetic Variation	[7]
SPARC	TTBQFM7	Strong	Genetic Variation	[8]
SOST	TTYRO4F	Definitive	Biomarker	[9]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
P3H1	DEW527E	Strong	Genetic Variation	[10]

This Disease Is Related to 34 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CCDC134	OT70OQQV	Limited	Autosomal recessive	[11]
TLL1	OTK9NM7G	Limited	Biomarker	[12]
KDELR2	OT9QW7Q0	Supportive	Autosomal dominant	[13]
MBTPS2	OT67CC7W	Supportive	Autosomal dominant	[14]
TENT5A	OTSYF511	Supportive	Autosomal dominant	[15]
MESD	OT3B2H8F	moderate	Genetic Variation	[16]
SUCO	OT3I9VO9	moderate	Biomarker	[17]
COL5A1	OT24078H	Strong	Genetic Variation	[18]
CREB3L1	OT2JHIHM	Strong	Genetic Variation	[19]
CRTAP	OT53H5U6	Strong	Genetic Variation	[20]
DLX3	OTARP5SQ	Strong	Biomarker	[21]
EFEMP2	OT0I2B4J	Strong	Genetic Variation	[22]
GPATCH8	OT43IH3F	Strong	Genetic Variation	[23]
GPR180	OT2P0XNK	Strong	Biomarker	[24]
IFITM5	OTLP5QEJ	Strong	Genetic Variation	[25]
MED18	OT6M6CQ8	Strong	Genetic Variation	[26]
P4HB	OTTYNYPF	Strong	Biomarker	[27]
PADI1	OT13WAQX	Strong	Altered Expression	[28]
PDIA2	OTC2WMXS	Strong	Altered Expression	[28]
PLA1A	OT2IXYNX	Strong	Biomarker	[29]
PLS3	OTYBM4PK	Strong	Biomarker	[28]
PNPLA2	OTR3ERMR	Strong	Biomarker	[7]
PPP1CB	OTYFTYFR	Strong	Genetic Variation	[30]
RNASE1	OTKZ7CO9	Strong	Biomarker	[31]
SEC24D	OTXR3KC9	Strong	Genetic Variation	[32]
SMAD4	OTWQWCKG	Strong	Biomarker	[33]
SMPD3	OTHQBETH	Strong	Biomarker	[34]
SP7	OT07ETZT	Strong	Genetic Variation	[35]
SRSF2	OTVDHO6U	Strong	Genetic Variation	[36]
TAPT1	OT3Z51KH	Strong	Biomarker	[37]
TMEM38B	OT9NOC9B	Strong	Genetic Variation	[38]
TNXB	OTVBWAV5	Strong	Genetic Variation	[39]
BGLAP	OTK1YLWQ	Definitive	Genetic Variation	[40]
NBAS	OTW9IBRI	Definitive	Genetic Variation	[41]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4448).
• [2] ClinicalTrials.gov (NCT05768854) An Open-label, Randomized, Active-Controlled, Phase 3 Study of Setrusumab Compared With Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta Types I, III or IV. U.S.National Institutes of Health.
• [3] Combination therapy in the Col1a2(G610C) mouse model of Osteogenesis Imperfecta reveals an additive effect of enhancing LRP5 signaling and inhibiting TGF signaling on trabecular bone but not on cortical bone.Bone. 2020 Feb;131:115084. doi: 10.1016/j.bone.2019.115084. Epub 2019 Oct 21.
• [4] Compound heterozygosity for a frameshift mutation and an upstream deletion that reduces expression of SERPINH1 in siblings with a moderate form of osteogenesis imperfecta.Am J Med Genet A. 2019 Aug;179(8):1466-1475. doi: 10.1002/ajmg.a.61170. Epub 2019 Jun 9.
• [5] Novel ActRIIB ligand trap increases muscle mass and improves bone geometry in a mouse model of severe osteogenesis imperfecta.Bone. 2019 Nov;128:115036. doi: 10.1016/j.bone.2019.115036. Epub 2019 Aug 13.
• [6] Novel mutations in BMP1 induce a rare type of osteogenesis imperfecta.Clin Chim Acta. 2019 Feb;489:21-28. doi: 10.1016/j.cca.2018.11.004. Epub 2018 Nov 5.
• [7] Novel mutations of the SERPINF1 and FKBP10 genes in Chinese families with autosomal recessive osteogenesis imperfecta.Int J Mol Med. 2018 Jun;41(6):3662-3670. doi: 10.3892/ijmm.2018.3542. Epub 2018 Mar 7.
• [8] Production and purification of recombinant human SPARC.Methods Cell Biol. 2018;143:335-345. doi: 10.1016/bs.mcb.2017.08.020. Epub 2017 Dec 1.
• [9] A xenograft model to evaluate the bone forming effects of sclerostin antibody in human bone derived from pediatric osteogenesis imperfecta patients.Bone. 2020 Jan;130:115118. doi: 10.1016/j.bone.2019.115118. Epub 2019 Oct 31.
• [10] Cellular stress due to impairment of collagen prolyl hydroxylation complex is rescued by the chaperone 4-phenylbutyrate.Dis Model Mech. 2019 Jun 20;12(6):dmm038521. doi: 10.1242/dmm.038521.
• [11] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [12] BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis.J Dent Res. 2017 May;96(5):578-585. doi: 10.1177/0022034516686558. Epub 2017 Jan 9.
• [13] Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2. Am J Hum Genet. 2020 Nov 5;107(5):989-999. doi: 10.1016/j.ajhg.2020.09.009. Epub 2020 Oct 13.
• [14] MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta. Nat Commun. 2016 Jul 6;7:11920. doi: 10.1038/ncomms11920.
• [15] FAM46A mutations are responsible for autosomal recessive osteogenesis imperfecta. J Med Genet. 2018 Apr;55(4):278-284. doi: 10.1136/jmedgenet-2017-104999. Epub 2018 Jan 22.
• [16] Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta. Am J Hum Genet. 2019 Oct 3;105(4):836-843. doi: 10.1016/j.ajhg.2019.08.008. Epub 2019 Sep 26.
• [17] Osteopotentia regulates osteoblast maturation, bone formation, and skeletal integrity in mice.J Cell Biol. 2010 May 3;189(3):511-25. doi: 10.1083/jcb.201003006.
• [18] Compound phenotype of osteogenesis imperfecta and Ehlers-Danlos syndrome caused by combined mutations in COL1A1 and COL5A1.Biosci Rep. 2019 Jul 25;39(7):BSR20181409. doi: 10.1042/BSR20181409. Print 2019 Jul 31.
• [19] A homozygous pathogenic missense variant broadens the phenotypic and mutational spectrum of CREB3L1-related osteogenesis imperfecta.Hum Mol Genet. 2019 Jun 1;28(11):1801-1809. doi: 10.1093/hmg/ddz017.
• [20] Identification of a Candidate Mutation in the COL1A2 Gene of a Chow Chow With Osteogenesis Imperfecta.J Hered. 2018 Mar 16;109(3):308-314. doi: 10.1093/jhered/esx074.
• [21] Osteogenesis imperfecta, tricho-dento-osseous syndrome and intellectual disability: a familial case with 17q21.33-q22 (COL1A1 and DLX3) deletion and 7q32.3-q33 duplication resulting from a reciprocal interchromosomal insertion.Am J Med Genet A. 2013 Oct;161A(10):2504-11. doi: 10.1002/ajmg.a.36122. Epub 2013 Aug 15.
• [22] Lethal osteogenesis imperfecta-like condition with cutis laxa and arterial tortuosity in MZ twins due to a homozygous fibulin-4 mutation.Pediatr Dev Pathol. 2012 Mar-Apr;15(2):137-41. doi: 10.2350/11-03-1010-CR.1. Epub 2011 Nov 9.
• [23] Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8.Hum Genet. 2011 Nov;130(5):671-83. doi: 10.1007/s00439-011-1006-9. Epub 2011 May 19.
• [24] Dual Interlocking Telescopic Rod Provides Effective Tibial Stabilization in Children With Osteogenesis Imperfecta.Clin Orthop Relat Res. 2018 Nov;476(11):2238-2246. doi: 10.1097/CORR.0000000000000429.
• [25] Oro-dental and cranio-facial characteristics of osteogenesis imperfecta type V.Eur J Med Genet. 2019 Dec;62(12):103606. doi: 10.1016/j.ejmg.2018.12.011. Epub 2018 Dec 26.
• [26] Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.Genet Med. 2016 Jun;18(6):570-6. doi: 10.1038/gim.2015.131. Epub 2015 Oct 1.
• [27] A novel missense mutation in P4HB causes mild osteogenesis imperfecta.Biosci Rep. 2019 Apr 30;39(4):BSR20182118. doi: 10.1042/BSR20182118. Print 2019 May 31.
• [28] NOVEL MUTATIONS IN THE WNT1, TMEM38B, P4HB, AND PLS3 GENES IN FOUR UNRELATED CHINESE FAMILIES WITH OSTEOGENESIS IMPERFECTA. Endocr Pract. 2019 Mar;25(3):230-241. doi: 10.4158/EP-2018-0443.
• [29] Type I procollagen C-propeptide defects: study of genotype-phenotype correlation and predictive role of crystal structure.Hum Mutat. 2014 Nov;35(11):1330-41. doi: 10.1002/humu.22677. Epub 2014 Oct 18.
• [30] Type 1 collagenopathy presenting with a Russell-Silver phenotype.Am J Med Genet A. 2011 Jun;155A(6):1414-8. doi: 10.1002/ajmg.a.33998. Epub 2011 May 12.
• [31] A single amino acid deletion in the alpha 2(I) chain of type I collagen produces osteogenesis imperfecta type III.Hum Genet. 1993 Feb;90(6):621-8. doi: 10.1007/BF00202479.
• [32] Japanese patient with Cole-carpenter syndrome with compound heterozygous variants of SEC24D.Am J Med Genet A. 2018 Dec;176(12):2882-2886. doi: 10.1002/ajmg.a.40643. Epub 2018 Nov 21.
• [33] Embryonic ablation of osteoblast Smad4 interrupts matrix synthesis in response to canonical Wnt signaling and causes an osteogenesis-imperfecta-like phenotype.J Cell Sci. 2013 Nov 1;126(Pt 21):4974-84. doi: 10.1242/jcs.131953. Epub 2013 Sep 4.
• [34] Neutral Sphingomyelinase 2 (SMPD3) Deficiency in Mice Causes Chondrodysplasia with Unimpaired Skeletal Mineralization.Am J Pathol. 2019 Sep;189(9):1831-1845. doi: 10.1016/j.ajpath.2019.05.008. Epub 2019 Jun 12.
• [35] Specificity Protein 7 Is Required for Proliferation and Differentiation of Ameloblasts and Odontoblasts.J Bone Miner Res. 2018 Jun;33(6):1126-1140. doi: 10.1002/jbmr.3401. Epub 2018 Mar 24.
• [36] Tracking COL1A1 RNA in osteogenesis imperfecta. splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain.J Cell Biol. 2000 Aug 7;150(3):417-32. doi: 10.1083/jcb.150.3.417.
• [37] Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia. Am J Hum Genet. 2015 Oct 1;97(4):521-34. doi: 10.1016/j.ajhg.2015.08.009. Epub 2015 Sep 10.
• [38] Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.J Clin Endocrinol Metab. 2017 Jun 1;102(6):2019-2028. doi: 10.1210/jc.2016-3766.
• [39] An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.Am J Med Genet A. 2016 Apr;170A(4):1080-5. doi: 10.1002/ajmg.a.37547. Epub 2016 Jan 22.
• [40] Metabolic phenotype in the mouse model of osteogenesis imperfecta.J Endocrinol. 2017 Sep;234(3):279-289. doi: 10.1530/JOE-17-0335. Epub 2017 Jul 17.
• [41] Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta. Bone. 2017 Jan;94:65-74. doi: 10.1016/j.bone.2016.10.023. Epub 2016 Oct 24.