Frequency
The prevalence of X-linked spondyloepiphyseal dysplasia tarda is estimated to be 1 in 150,000 to 200,000 people worldwide.
Causes
Mutations in the TRAPPC2 gene cause X-linked spondyloepiphyseal dysplasia tarda. The TRAPPC2 gene provides instructions for producing the protein sedlin. Sedlin is part of a large group of proteins called the trafficking protein particle (TRAPP) complex, which plays a role in the transport of proteins between various cell compartments (organelles). Research shows that sedlin is required for transporting large proteins out of the endoplasmic reticulum, which is an organelle that is involved in protein processing and transport. For example, sedlin is needed to move large molecules called procollagens out of the endoplasmic reticulum so they can be processed by enzymes to create smaller mature collagen proteins, which strengthen and support connective tissues, such as skin, bone, cartilage, tendons, and ligaments.
Almost all TRAPPC2 gene mutations that cause X-linked spondyloepiphyseal dysplasia tarda result in a nonfunctional sedlin protein. As a result, large proteins, including procollagen, cannot be transported out of the endoplasmic reticulum. A lack of procollagen transport results in a decrease in mature collagen in cells and impairs the development of bones, cartilage, and other connective tissues. It is likely that this disruption in bone development leads to many of the signs and symptoms of X-linked spondyloepiphyseal dysplasia tarda, although it is unclear why the skeletal problems do not appear until later in childhood.
In about 10 percent of affected males, an identified mutation in the TRAPPC2 gene is not found. The cause of the condition in these individuals is unknown.
Inheritance
X-linked spondyloepiphyseal dysplasia tarda is inherited in an X-linked recessive pattern. The TRAPPC2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a TRAPPC2 gene mutation may develop osteoarthritis in early adulthood.
Other Names for This Condition
- Late onset spondyloepiphyseal dysplasia
- SED tarda
- X-linked SED
- X-linked SEDT
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Fiedler J, Le Merrer M, Mortier G, Heuertz S, Faivre L, Brenner RE. X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families. Hum Mutat. 2004 Jul;24(1):103. doi: 10.1002/humu.9254. Citation on PubMed
- Gedeon AK, Tiller GE, Le Merrer M, Heuertz S, Tranebjaerg L, Chitayat D, Robertson S, Glass IA, Savarirayan R, Cole WG, Rimoin DL, Kousseff BG, Ohashi H, Zabel B, Munnich A, Gecz J, Mulley JC. The molecular basis of X-linked spondyloepiphyseal dysplasia tarda. Am J Hum Genet. 2001 Jun;68(6):1386-97. doi: 10.1086/320592. Epub 2001 May 8. Citation on PubMed or Free article on PubMed Central
- Ryu H, Park J, Chae H, Kim M, Kim Y, Ok IY. X-linked spondyloepiphyseal dysplasia tarda: Identification of a TRAPPC2 mutation in a Korean pedigree. Ann Lab Med. 2012 May;32(3):234-7. doi: 10.3343/alm.2012.32.3.234. Epub 2012 Apr 18. Citation on PubMed or Free article on PubMed Central
- Savarirayan R, Thompson E, Gecz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). Eur J Hum Genet. 2003 Sep;11(9):639-42. doi: 10.1038/sj.ejhg.5201025. Citation on PubMed
- Venditti R, Scanu T, Santoro M, Di Tullio G, Spaar A, Gaibisso R, Beznoussenko GV, Mironov AA, Mironov A Jr, Zelante L, Piemontese MR, Notarangelo A, Malhotra V, Vertel BM, Wilson C, De Matteis MA. Sedlin controls the ER export of procollagen by regulating the Sar1 cycle. Science. 2012 Sep 28;337(6102):1668-72. doi: 10.1126/science.1224947. Citation on PubMed or Free article on PubMed Central
- Xia XY, Cui YX, Zhou YC, Zhou X, Shi YC, Wei L, Li XJ, Huang YF, Huang TT. A novel insertion mutation in the SEDL gene results in X-linked spondyloepiphyseal dysplasia tarda in a large Chinese pedigree. Clin Chim Acta. 2009 Dec;410(1-2):39-42. doi: 10.1016/j.cca.2009.09.016. Epub 2009 Sep 19. Citation on PubMed
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