Details of Disease

General Information of Disease (ID: DISO4L5A)

• Disease Name: Spondyloepimetaphyseal dysplasia
• Synonyms: SEMD; spondylo-epi-(meta)-physeal dysplasia
• Definition: An osteochondrodysplasia that results in abnormalities of bone growth in the vertebral column, epiphysis, and metaphysis.
• Disease Hierarchy:
  DIS9SPWW: Osteochondrodysplasia
  DIS5Z8U6: Skeletal dysplasia
  DISO4L5A: Spondyloepimetaphyseal dysplasia
• Disease Identifiers:
  MONDO ID: MONDO_0100510
  UMLS CUI: C0432211
  MedGen ID: 609408
  HPO ID: HP:0002651
  SNOMED CT ID: 254062008

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MMP13	TTHY57M	Strong	Genetic Variation	[1]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACAN	OTUOCW8K	Limited	Genetic Variation	[2]
DDRGK1	OT3KCK0U	Limited	Biomarker	[3]
RSPRY1	OT9MVWO0	Limited	Biomarker	[4]
B3GALT6	OTF4HBAT	moderate	Genetic Variation	[5]
COL2A1	OT5E59C8	moderate	Biomarker	[6]
KIF22	OTY6X6BL	moderate	Genetic Variation	[7]
COL10A1	OTC4G2YC	Strong	Biomarker	[8]
COL9A2	OT1ZBDBV	Strong	Biomarker	[8]
COL9A3	OTCUJOEK	Strong	Biomarker	[8]
DYM	OTQ670WI	Strong	Biomarker	[9]
HAPLN1	OTXWR9TJ	Strong	Genetic Variation	[8]
MATN3	OTH9H74J	Strong	Genetic Variation	[10]
PAPSS2	OTDLEXPN	Strong	Genetic Variation	[11]
PISD	OTP9COQT	Strong	Genetic Variation	[12]
RPL13	OTFKNTD6	Strong	Genetic Variation	[13]

References

• [1] MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO). J Clin Invest. 2005 Oct;115(10):2832-42. doi: 10.1172/JCI22900.
• [2] The aggrecanopathies; an evolving phenotypic spectrum of human genetic skeletal diseases.Orphanet J Rare Dis. 2016 Jun 28;11(1):86. doi: 10.1186/s13023-016-0459-2.
• [3] 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.
• [4] 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.
• [5] Biallelic B3GALT6 mutations cause spondylodysplastic Ehlers-Danlos syndrome. Hum Mol Genet. 2018 Oct 15;27(20):3475-3487. doi: 10.1093/hmg/ddy234.
• [6] A new form of severe spondyloepimetaphyseal dysplasia: clinical and radiological characterization.Am J Med Genet A. 2013 Oct;161A(10):2645-51. doi: 10.1002/ajmg.a.36132. Epub 2013 Aug 16.
• [7] A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. Eur J Hum Genet. 2016 Aug;24(8):1206-10. doi: 10.1038/ejhg.2015.261. Epub 2015 Dec 16.
• [8] Linkage studies of a Missouri kindred with autosomal dominant spondyloepimetaphyseal dysplasia (SEMD) indicate genetic heterogeneity.J Bone Miner Res. 1997 Aug;12(8):1204-9. doi: 10.1359/jbmr.1997.12.8.1204.
• [9] Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans.Hum Mol Genet. 2015 May 15;24(10):2771-83. doi: 10.1093/hmg/ddv038. Epub 2015 Feb 4.
• [10] Multiple functions of the first EGF domain in matrilin-3: Secretion and endoplasmic reticulum stress.Int J Mol Med. 2015 Dec;36(6):1648-56. doi: 10.3892/ijmm.2015.2377. Epub 2015 Oct 15.
• [11] Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation.Eur J Hum Genet. 2005 May;13(5):541-6. doi: 10.1038/sj.ejhg.5201339.
• [12] The homozygous variant c.797G>A/p.(Cys266Tyr) in PISD is associated with a Spondyloepimetaphyseal dysplasia with large epiphyses and disturbed mitochondrial function. Hum Mutat. 2019 Mar;40(3):299-309. doi: 10.1002/humu.23693. Epub 2018 Dec 21.
• [13] RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature. Am J Hum Genet. 2019 Nov 7;105(5):1040-1047. doi: 10.1016/j.ajhg.2019.09.024. Epub 2019 Oct 17.