Details of Disease

Disease Name

Skeletal dysplasia

primary osteodysplasia; primary skeletal dysplasia; primary bone dysplasia; Mendelian skeletal dysplasia

Definition

Any Mendelian diseases that affects growth and development of the skeleton.

Disease Hierarchy

DISYKSRF: Genetic disease

DISE1F82: Bone disease

DIS5Z8U6: Skeletal dysplasia

Disease Identifiers

MONDO ID

MONDO_0018230

UMLS CUI

C0410528

MedGen ID

98053

HPO ID

HP:0002652

Orphanet ID

364526

SNOMED CT ID

105986008

General Information of Disease (ID: DIS5Z8U6)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EBP	TT4VQZX	Limited	Biomarker	[1]
FGFR3	TTST7KB	Limited	Genetic Variation	[2]
NAGLU	TTDM6HZ	Limited	Genetic Variation	[3]
NPR2	TTNB7IF	Limited	Genetic Variation	[4]
GDF5	TT37XV9	moderate	Genetic Variation	[5]
TRPV4	TTKP2SU	moderate	Genetic Variation	[6]
CTSK	TTDZN01	Strong	Genetic Variation	[7]
FLNA	TTSTRZY	Strong	Genetic Variation	[8]
LIFR	TTID542	Strong	Genetic Variation	[9]
PTH1R	TTFPD47	Strong	Genetic Variation	[10]
RUNX2	TTD6SZ8	Strong	Genetic Variation	[11]
THRA	TTTSEPU	Strong	Genetic Variation	[12]
NPPC	TTRK0B9	Definitive	Biomarker	[13]
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⏷ Show the Full List of 13 DTT(s)

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC35A3	DTB930Q	moderate	Genetic Variation	[14]
SLC10A7	DTG1RJO	Strong	Biomarker	[15]
SLC35D1	DTJ5CF0	Strong	Biomarker	[16]
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This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ACP5	DESITDW	Limited	Genetic Variation	[17]
CYP26B1	DEZT8FM	Limited	Biomarker	[3]
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This Disease Is Related to 34 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EFTUD2	OT3X7QG2	Limited	Biomarker	[18]
FZD2	OT952ML1	Limited	Genetic Variation	[19]
LFNG	OTPSUBN2	Limited	Genetic Variation	[20]
PISD	OTP9COQT	Limited	Biomarker	[21]
RSPRY1	OT9MVWO0	Limited	Biomarker	[22]
B3GAT3	OTDSN5XF	moderate	Genetic Variation	[23]
C2CD3	OTC52E7V	moderate	Genetic Variation	[24]
COL10A1	OTC4G2YC	moderate	Altered Expression	[25]
FGD3	OTIH6283	moderate	Biomarker	[26]
GNPTAB	OT2Z03OB	moderate	Genetic Variation	[27]
GYPB	OTESHUIX	moderate	Genetic Variation	[28]
GYPE	OTBHAG6A	moderate	Genetic Variation	[28]
KIF22	OTY6X6BL	moderate	Biomarker	[29]
MATN1	OTBRTCTQ	moderate	Genetic Variation	[30]
NKX3-2	OTH4NRH7	moderate	Biomarker	[31]
SBDS	OTHDCCIB	moderate	Genetic Variation	[32]
TRPS1	OT7XPPEL	moderate	Genetic Variation	[33]
AFF4	OTTL5Y8R	Strong	Genetic Variation	[34]
ALG9	OT5V9PIR	Strong	Genetic Variation	[35]
AMER1	OT8EFJPM	Strong	Genetic Variation	[36]
COL1A1	OTI31178	Strong	Genetic Variation	[37]
CSGALNACT1	OTBML9D9	Strong	Genetic Variation	[38]
DDRGK1	OT3KCK0U	Strong	Altered Expression	[39]
DMP1	OTBWBWW7	Strong	Genetic Variation	[40]
EXTL3	OT2BRUBN	Strong	Genetic Variation	[41]
KIAA0753	OTMFT2I9	Strong	Genetic Variation	[42]
LEMD3	OTILAM4I	Strong	Genetic Variation	[43]
SGMS2	OT3NHO99	Strong	Genetic Variation	[44]
SH3PXD2B	OTAOMCDJ	Strong	Biomarker	[45]
SHOX	OTE0YZJO	Strong	Genetic Variation	[46]
SMARCAL1	OTTKXLUZ	Strong	Genetic Variation	[47]
TMEM87B	OTXT7BCU	Strong	Genetic Variation	[48]
MAB21L2	OTZM5VMX	Definitive	Biomarker	[49]
POP1	OTBIYMJ0	Definitive	Genetic Variation	[50]
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⏷ Show the Full List of 34 DOT(s)

References

1	X-linked dominant chondrodysplasia punctata with severe phenotype in a female fetus: A case report.Medicine (Baltimore). 2019 Jan;98(1):e13850. doi: 10.1097/MD.0000000000013850.
2	Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia.Gene. 2018 Jan 30;641:355-360. doi: 10.1016/j.gene.2017.10.062. Epub 2017 Nov 6.
3	Mucopolysaccharidosis IIIB and mild skeletal anomalies: coexistence of NAGLU and CYP26B1 missense variations in the same patient in a Chinese family.BMC Med Genet. 2018 Apr 2;19(1):51. doi: 10.1186/s12881-018-0562-4.
4	Role of the natriuretic peptide system in normal growth and growth disorders.Horm Res Paediatr. 2014;82(4):222-9. doi: 10.1159/000365049. Epub 2014 Sep 3.
5	Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. J Hum Genet. 2008;53(4):368-374. doi: 10.1007/s10038-008-0253-7. Epub 2008 Feb 19.
6	A channelopathy mechanism revealed by direct calmodulin activation of TrpV4.Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9400-5. doi: 10.1073/pnas.1510602112. Epub 2015 Jul 13.
7	Cathepsin K: isolation and characterization of the murine cDNA and genomic sequence, the homologue of the human pycnodysostosis gene.Biochem Mol Med. 1996 Dec;59(2):200-6. doi: 10.1006/bmme.1996.0088.
8	A recurrent mutation causing Melnick-Needles syndrome in females confers a severe, lethal phenotype in males.Am J Med Genet A. 2018 Apr;176(4):980-984. doi: 10.1002/ajmg.a.38651.
9	Non-truncating LIFR mutation: causal for prominent congenital pain insensitivity phenotype with progressive vertebral destruction?.Clin Genet. 2016 Feb;89(2):210-6. doi: 10.1111/cge.12657. Epub 2015 Sep 29.
10	Report of second case and clinical and molecular characterization of Eiken syndrome.Clin Genet. 2018 Nov;94(5):457-460. doi: 10.1111/cge.13413. Epub 2018 Jul 27.
11	Metabolomics profiling of cleidocranial dysplasia.Clin Oral Investig. 2019 Mar;23(3):1031-1040. doi: 10.1007/s00784-018-2496-9. Epub 2018 Jun 25.
12	Contrasting Phenotypes in Resistance to Thyroid Hormone Alpha Correlate with Divergent Properties of Thyroid Hormone Receptor 1 Mutant Proteins.Thyroid. 2017 Jul;27(7):973-982. doi: 10.1089/thy.2017.0157.
13	Exogenous C-type natriuretic peptide restores normal growth and prevents early growth plate closure in its deficient rats.PLoS One. 2018 Sep 20;13(9):e0204172. doi: 10.1371/journal.pone.0204172. eCollection 2018.
14	A human case of SLC35A3-related skeletal dysplasia.Am J Med Genet A. 2017 Oct;173(10):2758-2762. doi: 10.1002/ajmg.a.38374. Epub 2017 Aug 4.
15	Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation. Hum Mol Genet. 2018 Sep 1;27(17):3029-3045. doi: 10.1093/hmg/ddy213.
16	Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. Nat Med. 2007 Nov;13(11):1363-7. doi: 10.1038/nm1655. Epub 2007 Oct 21.
17	Craniofacial anomalies associated with spondyloenchondrodysplasia: Two case reports.Medicine (Baltimore). 2018 Dec;97(50):e13644. doi: 10.1097/MD.0000000000013644.
18	EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway.Hum Genomics. 2019 Dec 5;13(1):63. doi: 10.1186/s40246-019-0238-y.
19	Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes.Am J Med Genet A. 2018 Mar;176(3):739-742. doi: 10.1002/ajmg.a.38623. Epub 2018 Jan 31.
20	Screening of known disease genes in congenital scoliosis.Mol Genet Genomic Med. 2018 Nov;6(6):966-974. doi: 10.1002/mgg3.466. Epub 2018 Sep 9.
21	PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes.Life Sci Alliance. 2019 Mar 11;2(2):e201900353. doi: 10.26508/lsa.201900353. Print 2019 Apr.
22	Further delineation of spondyloepimetaphyseal dysplasia Faden-Alkuraya type: A RSPRY1-associated spondylo-epi-metaphyseal dysplasia with cono-brachydactyly and craniosynostosis.Am J Med Genet A. 2018 Sep;176(9):2009-2016. doi: 10.1002/ajmg.a.40427. Epub 2018 Jul 31.
23	Skeletal dysplasia in a consanguineous clan from the island of Nias/Indonesia is caused by a novel mutation in B3GAT3.Hum Genet. 2015 Jul;134(7):691-704. doi: 10.1007/s00439-015-1549-2. Epub 2015 Apr 19.
24	Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function.Sci Rep. 2016 Apr 20;6:24083. doi: 10.1038/srep24083.
25	Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.J Clin Invest. 2017 Oct 2;127(10):3861-3865. doi: 10.1172/JCI93094. Epub 2017 Sep 18.
26	Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle.PLoS Genet. 2015 Aug 25;11(8):e1005433. doi: 10.1371/journal.pgen.1005433. eCollection 2015 Aug.
27	Prenatal skeletal dysplasia phenotype in severe MLII alpha/beta with novel GNPTAB mutation.Gene. 2014 Jun 1;542(2):266-8. doi: 10.1016/j.gene.2014.03.053. Epub 2014 Mar 28.
28	Omphalocele and multiple severe congenital anomalies associated with osteodysplasty (Melnick-Needles syndrome).Am J Med Genet. 1982 Dec;13(4):453-63. doi: 10.1002/ajmg.1320130416.
29	Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity. Am J Hum Genet. 2011 Dec 9;89(6):767-72. doi: 10.1016/j.ajhg.2011.10.016.
30	Matrix composition of cartilaginous anlagen in achondrogenesis type II (Langer-Saldino).Front Biosci. 2005 Jan 1;10:446-53. doi: 10.2741/1540. Print 2005 Jan 1.
31	Sequence and chromosomal assignment of human BAPX1, a bagpipe-related gene, to 4p16.1: a candidate gene for skeletal dysplasia.Genomics. 1997 Oct 15;45(2):425-8. doi: 10.1006/geno.1997.4926.
32	The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type.J Med Genet. 2007 Apr;44(4):e73. doi: 10.1136/jmg.2006.043869.
33	Uncoupling of chondrocyte differentiation and perichondrial mineralization underlies the skeletal dysplasia in tricho-rhino-phalangeal syndrome.Hum Mol Genet. 2008 Jul 15;17(14):2244-54. doi: 10.1093/hmg/ddn125. Epub 2008 Apr 17.
34	Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat Genet. 2015 Apr;47(4):338-44. doi: 10.1038/ng.3229. Epub 2015 Mar 2.
35	A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach-Nishimura skeletal dysplasia due to pathogenic variants in ALG9.Eur J Hum Genet. 2016 Feb;24(2):198-207. doi: 10.1038/ejhg.2015.91. Epub 2015 May 13.
36	Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet. 2009 Jan;41(1):95-100. doi: 10.1038/ng.270. Epub 2008 Dec 14.
37	Diagnostic conundrums in antenatal presentation of a skeletal dysplasia with description of a heterozygous C-propeptide mutation in COL1A1 associated with a severe presentation of osteogenesis imperfecta.Am J Med Genet A. 2016 Dec;170(12):3303-3307. doi: 10.1002/ajmg.a.37943. Epub 2016 Aug 23.
38	CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.Hum Mutat. 2020 Mar;41(3):655-667. doi: 10.1002/humu.23952. Epub 2019 Dec 3.
39	Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia. J Clin Invest. 2017 Apr 3;127(4):1475-1484. doi: 10.1172/JCI90193. Epub 2017 Mar 6.
40	Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.J Bone Miner Res. 2010 Oct;25(10):2165-74. doi: 10.1002/jbmr.105.
41	Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome. Am J Hum Genet. 2017 Feb 2;100(2):281-296. doi: 10.1016/j.ajhg.2017.01.013. Epub 2017 Jan 26.
42	Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies.Sci Rep. 2017 Nov 14;7(1):15585. doi: 10.1038/s41598-017-15442-1.
43	Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS.Bone. 2017 Aug;101:145-155. doi: 10.1016/j.bone.2017.04.010. Epub 2017 Apr 21.
44	Osteoporosis and skeletal dysplasia caused by pathogenic variants in SGMS2. JCI Insight. 2019 Apr 4;4(7):e126180. doi: 10.1172/jci.insight.126180. eCollection 2019 Apr 4.
45	Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome. Am J Hum Genet. 2010 Feb 12;86(2):254-61. doi: 10.1016/j.ajhg.2010.01.009. Epub 2010 Feb 4.
46	Retinoic acid catabolizing enzyme CYP26C1 is a genetic modifier in SHOX deficiency.EMBO Mol Med. 2016 Dec 1;8(12):1455-1469. doi: 10.15252/emmm.201606623. Print 2016 Dec.
47	Chromatin changes in SMARCAL1 deficiency: A hypothesis for the gene expression alterations of Schimke immuno-osseous dysplasia.Nucleus. 2016 Nov;7(6):560-571. doi: 10.1080/19491034.2016.1255835.
48	Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy.Cold Spring Harb Mol Case Stud. 2016 May;2(3):a000844. doi: 10.1101/mcs.a000844.
49	Generation and characterization of pathogenic Mab21l2(R51C) mouse model.Genesis. 2018 Dec;56(11-12):e23261. doi: 10.1002/dvg.23261. Epub 2018 Nov 29.
50	Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia.Clin Genet. 2017 Jul;92(1):91-98. doi: 10.1111/cge.12964. Epub 2017 Feb 22.