Alternative titles; symbols
SNOMEDCT: 51952004; ORPHA: 93284; DO: 0080362;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xp22.2 | Spondyloepiphyseal dysplasia tarda | 313400 | X-linked recessive | 3 | TRAPPC2 | 300202 |
A number sign (#) is used with this entry because spondyloepiphyseal dysplasia tarda is caused by mutation in the SEDL (TRAPPC2) gene (300202) on chromosome Xp22.
Bannerman et al. (1971) cited early reports of this disorder (e.g., Nilsonne, 1927; Barber, 1960) and reviewed the clinical features in a large American family of English origin originally described by Jacobsen (1939). They described the major features of the disorder as short stature first evident between 5 and 14 years of age; shortness due to impaired growth of the spine; radiologically, characteristic flattening of vertebrae with central humping; dysplastic changes of femoral heads and neck; and minor changes in other bones. Bony changes lead to secondary osteoarthritis, which becomes troublesome in the forties and may be disabling in the sixties. Bannerman (1981) reviewed this material and concluded that heterozygotes show no abnormality such as short stature. Several females had arthritic complaints; e.g., M.Z., the daughter and mother of affected males, had considerable 'arthritis' from age 33 years and by age 51 had almost no movement in either hip and, by x-ray, bony fusion of the left hip.
The radiographic features of this disorder are so distinctive that the diagnosis seems unequivocal in the sexually normal, 29-year-old woman (with normal XX karyotype including banding) reported by Monteiro de Pina Neto et al. (1982). No other persons in the family were affected. The authors suggested that she was heterozygous and that chance lyonization of most X chromosomes with the normal allele had occurred.
Heuertz et al. (1993) suggested that this disorder was first described by Maroteaux et al. (1957) in a study of 3 large kindreds with 11 affected persons. The disorder is characterized by short stature which becomes evident between 10 and 14 years of age and leads to an average adult height of 1.45 m. Radiologic diagnosis cannot be established before 4 to 6 years of age. Bone changes of the femoral head lead to secondary osteoarthritis during adulthood and some patients require total arthroplasty of the hip before the age of 40 years.
Whyte et al. (1999) described the clinical and radiographic evaluation of a second large American kindred with X-linked recessive SEDT, the first such family being the classic family reported by Jacobsen (1939).
Wynne-Davies and Gormley (1985) estimated the prevalence of SEDT to be 1 per 100,000 in a Scottish population.
Cosegregation of SEDT and deutan colorblindness (303800) suggested to Kousseff et al. (1986) that the SEDT locus is in the Xq28 band. Szpiro-Tapia et al. (1988) excluded linkage with markers in region Xq28. They found linkage to DXS41 (maximum lod = 3.07 at theta = 0.08), located in Xp22.1, and DXS92 (maximum lod = 2.95 at theta = 0.05). DXS92 had been thought to be located at Xq26-q27; hybridization to cells containing X chromosome fragments, however, excluded location on Xq and on the proximal part of Xp. Szpiro-Tapia et al. (1988) concluded that DXS92 is located on Xp between Xp11.21 and Xpter. Reference was made to another family with linkage mapping to the same region of Xp. It is of interest that Bannerman et al. (1971), studying the original family reported by Jacobsen (1939) in Buffalo, found a suggestion of linkage to Xg blood group, which would be consistent with the findings of the recent study.
Heuertz et al. (1993) extended the studies of Szpiro-Tapia et al. (1988) by analyzing 15 families with 13 markers from the Xp22 region. Multipoint linkage analysis indicated that the SEDT mutation is located between DXS16 and DXS92.
Bernard et al. (1996) presented linkage data using microsatellite markers on 2 Canadian X-linked SED families, one of Norwegian descent and the other from Great Britain. Support of the previous localization was obtained. One family showed a maximal lod score of 3.0 at theta = 0.0 with marker DXS1043 and the other family had a maximal lod score of 1.2 at theta = 0.0 with markers DXS1224 and DXS418.
Gedeon et al. (1999) confirmed and refined the localization of SEDT to an interval of less than 170 kb by critical recombination events at DXS16 and AFMa124wc1 in 2 families.
Venditti et al. (2012) found that TANGO1 (613455) recruits sedlin (300202), a TRAPP component that is defective in spondyloepiphyseal dysplasia tarda, and that sedlin is required for the endoplasmic reticulum (ER) export of procollagen, prefibrils of which are too large to fit into typical COPII vesicles. Sedlin bound and promoted efficient cycling of SAR1 (603379), a guanosine triphosphate that can constrict membranes, and thus allowed nascent carriers to grow and incorporate procollagen prefibrils. This joint action of TANGO1 and Sedlin sustained the ER export of procollagen, and its derangement may explain the defective chondrogenesis underlying SEDT.
Gedeon et al. (1999) detected 3 dinucleotide deletions in the SEDL gene (300202.0001-300202.0003), resulting in frameshifts and premature stop codons, in 3 Australian families with SEDT.
In an Ashkenazi Jewish family with SEDT, Bar-Yosef et al. (2004) identified a single nucleotide deletion at position 613 in the SEDL gene (300202.0011). The authors stated that this was the first report of an SEDL mutation in a Jewish family.
Bannerman, R. M., Ingall, G. B., Mohn, J. F. X-linked spondyloepiphyseal dysplasia tarda: clinical and linkage data. J. Med. Genet. 8: 291-301, 1971. [PubMed: 4999590] [Full Text: https://doi.org/10.1136/jmg.8.3.291]
Bannerman, R. M. X-linked spondyloepiphyseal dysplasia tarda (SDT). Birth Defects Orig. Art. Ser. V(4): 48-51, 1969.
Bannerman, R. M. Personal Communication. Buffalo, N. Y. 10/13/1981.
Bar-Yosef, U., Ohana, E., Hershkovitz, E., Perlmuter, S., Ofir, R., Birk, O. S. X-linked spondyloepiphyseal dysplasia tarda: a novel SEDL mutation in a Jewish Ashkenazi family and clinical intervention considerations. Am. J. Med. Genet. 125A: 45-48, 2004. [PubMed: 14755465] [Full Text: https://doi.org/10.1002/ajmg.a.20435]
Barber, H. S. An unusual form of familial osteodystrophy. Lancet 275: 1220-1221, 1960. Note: Originally Volume I. [PubMed: 13796581] [Full Text: https://doi.org/10.1016/s0140-6736(60)91101-6]
Barber, H. S. An unusual form of familial osteodystrophy. (Letter) Lancet 276: 154-155, 1960. Note: Originally Volume II.
Bernard, L. E., Chitayat, D., Weksberg, R., Van Allen, M. I., Langlois, S. Linkage analysis of two Canadian families segregating for X linked spondyloepiphyseal dysplasia. J. Med. Genet. 33: 432-434, 1996. [PubMed: 8733060] [Full Text: https://doi.org/10.1136/jmg.33.5.432]
Branford, W. A., Beveridge, G. W., Wynne-Davies, R. Two first cousins with spondyloepiphyseal dysplasia tarda (X linked recessive form), one also with poikiloderma atrophicans vasculare progressing to lymphocytic lymphoma. J. Med. Genet. 19: 210-213, 1982. [PubMed: 6809944] [Full Text: https://doi.org/10.1136/jmg.19.3.210]
Gedeon, A. K., Colley, A., Jamieson, R., Thompson, E. M., Rogers, J., Sillence, D., Tiller, G. E., Mulley, J. C., Gecz, J. Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nature Genet. 22: 400-404, 1999. [PubMed: 10431248] [Full Text: https://doi.org/10.1038/11976]
Heuertz, S., Nelen, M., Wilkie, A. O. M., Le Merrer, M., Delrieu, O., Larget-Piet, L., Tranebjaerg, L., Bick, D., Hamel, B., Van Oost, B. A., Maroteaux, P., Hors-Cayla, M.-C. The gene for spondyloepiphyseal dysplasia (SEDL) maps to Xp22 between DXS16 and DXS92. Genomics 18: 100-104, 1993. [PubMed: 7903956] [Full Text: https://doi.org/10.1006/geno.1993.1431]
Hobaek, A. Problems of Hereditary Chondrodysplasia. Oslo: Oslo Univ. Press (pub.) 1961.
Iceton, J. A., Horne, G. Spondylo-epiphyseal dysplasia tarda: the X-linked variety in three brothers. J. Bone Joint Surg. Br. 68: 616-619, 1986. [PubMed: 3733841] [Full Text: https://doi.org/10.1302/0301-620X.68B4.3733841]
Jacobsen, A. W. Hereditary osteochondro-dystrophia deformans: a family with twenty members affected in five generations. JAMA 113: 121-124, 1939.
Kousseff, B. G., Hummel, M., Phillips, J., III, Murphy, P. Spondyloepiphyseal dysplasia tarda and deutan color blindness in a family. (Abstract) 7th International Congress of Human Genetics, Berlin 1986. P. 258.
Lamy, M., Maroteaux, P. Les chondrodystrophies genotypiques. Paris: L'Expansion (pub.) 1960. P. 67ff.
Langer, L. O., Jr. Spondyloepiphyseal dysplasia tarda: hereditary chondrodysplasia with characteristic vertebral configuration in the adult. Radiology 82: 833-839, 1964. [PubMed: 14153674] [Full Text: https://doi.org/10.1148/82.5.833]
Maroteaux, P., Lamy, M., Bernard, J. La dysplasie spondylo-epiphysaire tardive. Presse Med. 65: 1205-1208, 1957. [PubMed: 13453331]
Monteiro de Pina Neto, J., Bonfim, M. D., Ferrari, I. Classic X-linked spondyloepiphyseal dysplasia tarda in a woman with normal karyotype. In: Papadatos, C. J.; Bartsocas, C. S.: Skeletal Dysplasias. New York: Alan R. Liss (pub.) 1982. Pp. 127-132.
Nilsonne, H. Eigentuemliche Wirbelkorper-veraenderungen mit familiaerem Auftreten. Acta Chir. Scand. 62: 550-554, 1927.
Szpiro-Tapia, S., Sefiani, A., Guilloud-Bataille, M., Heuertz, S., LeMarec, B., Frezal, J., Maroteaux, P., Hors-Cayla, M. C. Spondyloepiphyseal dysplasia tarda: linkage with genetic markers from the distal short arm of the X chromosome. Hum. Genet. 81: 61-63, 1988. [PubMed: 3198127] [Full Text: https://doi.org/10.1007/BF00283731]
Venditti, R., Scanu, T., Santoro, M., Di Tullio, G., Spaar, A., Gaibisso, R., Beznoussenko, G. V., Mironov, A. A., Mironov, A., Jr., Zelante, L., Piemontese, M. R., Notarangelo, A., Malhotra, V., Vertel, B. M., Wilson, C., De Matteis, M. A. Sedlin controls the ER export of procollagen by regulating the Sar1 cycle. Science 337: 1668-1672, 2012. [PubMed: 23019651] [Full Text: https://doi.org/10.1126/science.1224947]
Whyte, M. P., Gottesman, G. S., Eddy, M. C., McAlister, W. H. X-linked recessive spondyloepiphyseal dysplasia tarda: clinical and radiographic evolution in a 6-generation kindred and review of the literature. Medicine 78: 9-25, 1999. [PubMed: 9990351] [Full Text: https://doi.org/10.1097/00005792-199901000-00002]
Wynne-Davies, R., Gormley, J. The prevalence of skeletal dysplasias: an estimate of their minimum frequency and the number of patients requiring orthopaedic care. J. Bone Joint Surg. Br. 67: 133-137, 1985. [PubMed: 3155744] [Full Text: https://doi.org/10.1302/0301-620X.67B1.3155744]