Details of Disease

General Information of Disease (ID: DIS9EL3M)

• Disease Name: Spondyloepiphyseal dysplasia tarda, X-linked
• Synonyms: spondyloepiphyseal dysplasia, late; SED; SEDT; spondyloepiphyseal dysplasia tarda X-linked; X linked spondyloepiphyseal dysplasia tarda; Sed tarda, X-linked; X-linked spondyloepiphyseal dysplasia; spondyloepiphyseal dysplasia tarda, X-linked recessive; spondyloepiphyseal dysplasia tarda, X-linked
• Definition: X-linked spondyloepiphyseal dysplasia tarda is an inherited skeletal disorder that affects males only. Physical characteristics include moderate short-stature (dwarfism); moderate to severe spinal deformities; barrel-chest; disproportionately short trunk and neck;disproportionatelylong arms,and premature osteoarthritis, especially in the hip joints. Final male adult height ranges from 4 feet 10 inches to 5 feet 6 inches. Other skeletal features of this condition include decreased mobility of the elbow and hip joints, arthritis, and abnormalities of the hip joint which causes the upper leg bones to turn inward. This condition is caused by mutations in the TRAPPC2 gene and is inherited in an X-linked recessive pattern.
• Disease Hierarchy:
  DISKGY38: Spondyloepiphyseal dysplasia tarda
  DIS3PN9X: X-linked disease
  DIS9EL3M: Spondyloepiphyseal dysplasia tarda, X-linked
• Disease Identifiers:
  MONDO ID: MONDO_0010737
  MESH ID: D010009
  UMLS CUI: C3541456
  OMIM ID: 313400
  MedGen ID: 762085
  SNOMED CT ID: 51952004

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
DLL3	TT1C9K6	Limited	Biomarker	[1]
FLT1	TT1VAUK	Limited	Biomarker	[2]
GLB1	TTNGJPH	Limited	Biomarker	[3]
KDR	TTUTJGQ	Limited	Biomarker	[2]
TRPV4	TTKP2SU	Disputed	Biomarker	[4]
FLNA	TTSTRZY	Strong	Biomarker	[5]
HSPG2	TT5UM29	Strong	Biomarker	[6]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHST3	DEQIZP2	Limited	Biomarker	[7]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
COL11A1	OTB0DRMS	Limited	Biomarker	[8]
ADAMTSL2	OTAXNV2U	Strong	Biomarker	[9]
COL2A1	OT5E59C8	Strong	Genetic Variation	[10]
COL9A1	OTWBR27Y	Strong	Biomarker	[11]
STX5	OTQ0024B	Strong	Genetic Variation	[12]
TRAPPC9	OTF0CVMC	Strong	Genetic Variation	[13]
TRAPPC2	OTWL5H45	Definitive	X-linked recessive	[14]

References

• [1] Mapping of the autosomal recessive (AR) craniometaphyseal dysplasia locus to chromosome region 6q21-22 and confirmation of genetic heterogeneity for mild AR spondylocostal dysplasia.Am J Med Genet. 2000 Dec 18;95(5):482-91. doi: 10.1002/1096-8628(20001218)95:5<482::aid-ajmg14>3.0.co;2-x.
• [2] Thiram-induced changes in the expression of genes relating to vascularization and tibial dyschondroplasia.Poult Sci. 2007 Nov;86(11):2390-5. doi: 10.3382/ps.2007-00219.
• [3] Spondyloepiphyseal dysplasia, corneal clouding, normal intelligence and acid beta-galactosidase deficiency.Clin Genet. 1976 May;9(5):495-504. doi: 10.1111/j.1399-0004.1976.tb01603.x.
• [4] Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nat Genet. 2008 Aug;40(8):999-1003. doi: 10.1038/ng.166. Epub 2008 Jun 29.
• [5] Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003 Apr;33(4):487-91. doi: 10.1038/ng1119. Epub 2003 Mar 3.
• [6] Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene. Nat Genet. 2001 Apr;27(4):431-4. doi: 10.1038/86941.
• [7] Whole exome sequencing detects CHST3 mutation in patient with acute promyelocytic leukemia: A case report.Medicine (Baltimore). 2018 Sep;97(36):e12214. doi: 10.1097/MD.0000000000012214.
• [8] Craniofacial cartilage morphogenesis requires zebrafish col11a1 activity.Matrix Biol. 2009 Oct;28(8):490-502. doi: 10.1016/j.matbio.2009.07.004. Epub 2009 Jul 26.
• [9] ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet. 2008 Sep;40(9):1119-23. doi: 10.1038/ng.199.
• [10] A single base mutation in the type II procollagen gene (COL2A1) that converts glycine alpha 1-247 to serine in a family with late-onset spondyloepiphyseal dysplasia.Hum Mutat. 1994;3(3):261-7. doi: 10.1002/humu.1380030314.
• [11] A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006 Sep;79(3):449-57. doi: 10.1086/506478. Epub 2006 Jun 26.
• [12] A trs20 mutation that mimics an SEDT-causing mutation blocks selective and non-selective autophagy: a model for TRAPP III organization.Traffic. 2013 Oct;14(10):1091-104. doi: 10.1111/tra.12095. Epub 2013 Aug 15.
• [13] The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated SEDT and TRAPPC9-associated congenital intellectual disability.PLoS One. 2011;6(8):e23350. doi: 10.1371/journal.pone.0023350. Epub 2011 Aug 15.
• [14] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.