Abstract
Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome with associated visceral and skeletal abnormalities. Alterations in the glypican-3 gene (GPC3), which is located on Xq26, have been implicated in the etiology of relatively milder cases of this disorder. Not all individuals with SGBS have demonstrated disruptions of the GPC3 locus, which raises the possibility that other loci on the X chromosome could be responsible for some cases of this syndrome. We have previously described a large family with a severe form of SGBS that is characterized by multiple anomalies, hydrops fetalis, and death within the first 8 wk of life. Using 25 simple tandem-repeat polymorphism markers spanning the X chromosome, we have localized the gene for this disorder to an approximately 6-Mb region of Xp22, with a maximum LOD score of 3.31 and with LOD scores <-2.0 for all of Xq. These results demonstrate that neither the GPC3 gene nor other genes on Xq26 are responsible for all cases of SGBS and that a second SGBS locus resides on Xp22.
Full Text
The Full Text of this article is available as a PDF (192.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cottingham R. W., Jr, Idury R. M., Schäffer A. A. Faster sequential genetic linkage computations. Am J Hum Genet. 1993 Jul;53(1):252–263. [PMC free article] [PubMed] [Google Scholar]
- Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
- Ferrero G. B., Franco B., Roth E. J., Firulli B. A., Borsani G., Delmas-Mata J., Weissenbach J., Halley G., Schlessinger D., Chinault A. C. An integrated physical and genetic map of a 35 Mb region on chromosome Xp22.3-Xp21.3. Hum Mol Genet. 1995 Oct;4(10):1821–1827. doi: 10.1093/hmg/4.10.1821. [DOI] [PubMed] [Google Scholar]
- Huber R., Mazzarella R., Chen C. N., Chen E., Ireland M., Lindsay S., Pilia G., Crisponi L. Glypican 3 and glypican 4 are juxtaposed in Xq26.1. Gene. 1998 Dec 28;225(1-2):9–16. doi: 10.1016/s0378-1119(98)00549-6. [DOI] [PubMed] [Google Scholar]
- Hughes-Benzie R. M., Hunter A. G., Allanson J. E., Mackenzie A. E. Simpson-Golabi-Behmel syndrome associated with renal dysplasia and embryonal tumor: localization of the gene to Xqcen-q21. 1992 Apr 15-May 1Am J Med Genet. 43(1-2):428–435. doi: 10.1002/ajmg.1320430165. [DOI] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li M., Squire J. A., Weksberg R. Overgrowth syndromes and genomic imprinting: from mouse to man. Clin Genet. 1998 Mar;53(3):165–170. [PubMed] [Google Scholar]
- Lindsay S., Ireland M., O'Brien O., Clayton-Smith J., Hurst J. A., Mann J., Cole T., Sampson J., Slaney S., Schlessinger D. Large scale deletions in the GPC3 gene may account for a minority of cases of Simpson-Golabi-Behmel syndrome. J Med Genet. 1997 Jun;34(6):480–483. doi: 10.1136/jmg.34.6.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neri G., Gurrieri F., Zanni G., Lin A. Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome. Am J Med Genet. 1998 Oct 2;79(4):279–283. doi: 10.1002/(sici)1096-8628(19981002)79:4<279::aid-ajmg9>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
- Opitz J. M., Herrmann J., Gilbert E. F., Matalon R. Simpson-Golabi-Behmel syndrome: follow-up of the Michigan family. Am J Med Genet. 1988 May-Jun;30(1-2):301–308. doi: 10.1002/ajmg.1320300131. [DOI] [PubMed] [Google Scholar]
- Opitz J. M. The Golabi-Rosen syndrome--report of a second family. Am J Med Genet. 1984 Jan;17(1):359–366. doi: 10.1002/ajmg.1320170129. [DOI] [PubMed] [Google Scholar]
- Orth U., Gurrieri F., Behmel A., Genuardi M., Cremer M., Gal A., Neri G. Gene for Simpson-Golabi-Behmel syndrome is linked to HPRT in Xq26 in two European families. Am J Med Genet. 1994 May 1;50(4):388–390. doi: 10.1002/ajmg.1320500423. [DOI] [PubMed] [Google Scholar]
- Pilia G., Hughes-Benzie R. M., MacKenzie A., Baybayan P., Chen E. Y., Huber R., Neri G., Cao A., Forabosco A., Schlessinger D. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996 Mar;12(3):241–247. doi: 10.1038/ng0396-241. [DOI] [PubMed] [Google Scholar]
- Schäffer A. A., Gupta S. K., Shriram K., Cottingham R. W., Jr Avoiding recomputation in linkage analysis. Hum Hered. 1994 Jul-Aug;44(4):225–237. doi: 10.1159/000154222. [DOI] [PubMed] [Google Scholar]
- Simpson J. L., Landey S., New M., German J. A previously unrecognized X-linked syndrome of dysmorphia. Birth Defects Orig Artic Ser. 1975;11(2):18–24. [PubMed] [Google Scholar]
- Terespolsky D., Farrell S. A., Siegel-Bartelt J., Weksberg R. Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis. Am J Med Genet. 1995 Nov 20;59(3):329–333. doi: 10.1002/ajmg.1320590310. [DOI] [PubMed] [Google Scholar]
- Veugelers M., Vermeesch J., Watanabe K., Yamaguchi Y., Marynen P., David G. GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome. Genomics. 1998 Oct 1;53(1):1–11. doi: 10.1006/geno.1998.5465. [DOI] [PubMed] [Google Scholar]
- Xuan J. Y., Besner A., Ireland M., Hughes-Benzie R. M., MacKenzie A. E. Mapping of Simpson-Golabi-Behmel syndrome to Xq25-q27. Hum Mol Genet. 1994 Jan;3(1):133–137. doi: 10.1093/hmg/3.1.133. [DOI] [PubMed] [Google Scholar]