Simpson-Golabi-Behmel Syndrome

Inheritance

X-linked with heterogeneity ; most families map Xq26 ; one large pedigree maps to Xp22

Clinics

Phenotype and clinics

Characterized by a wide variety of clinical manifestations including pre-natal and post-natal overgrowth syndrome SGBS is phenotypically similar to Beckwith-Wiedemann syndrome (BWS) suggesting that at least part of the SGBS phenotype could be due to increased IGF-II signalling. Xq26: coarse facieses with mandibular overgrowth, cleft palate, heart defects, hernias, supernumerary nipples, renal and skeletal abnormalities. Xp22: lethal form, multiple anomalies, hydrops fetalis, death within first 8 weeks of life.

Neoplastic risk

increased risk of embryonal tumors, including Wilms tumor, neuroblastoma ; one case of hepatocellular carcinoma reported

Genes involved and Proteins

 

Gene Name	glypican-3 (GPC3)
Location	Xq26

Protein
Description	GPC3 is highly expressed in embryonal tissues such as the developing intestine and the mesoderm-derived tissues, and its expression is downregulated in most adult tissue, implying a potential role in development. GPC3 is a heparan sulfate proteoglycan (HSPG) that is attached to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor.
Function	HSPGs of the cell surface are highly interactive macromolecules playing various roles in cell migration, proliferation, differentiation and adhesion, and participating in many developmental and pathological processes.

Mutations

Germinal

Most cases are caused by deletions of different exons in the GPC3 genes . The exact role of GPC3 in the etiology of SGBS is still unknown. The renal dysplasia observed in both SGBS patients and GPC3-deficient mice could be explained by the participation of GPC3 in the control of renal branching morphogenesis by modulating the actions of several different growth factors, including BMP2, BMP7 and fibroblast growth factor 7.

External links

OMIM	312870
Orphanet	Simpson-Golabi-Behmel syndrome

Bibliography

Simpson-Golabi-Behmel syndrome associated with renal dysplasia and embryonal tumor: localization of the gene to Xqcen-q21.

Hughes-Benzie RM, Hunter AG, Allanson JE, Mackenzie AE

American journal of medical genetics. 1992 ; 43 (1-2) : 428-435.

PMID 1605222

Integral membrane heparan sulfate proteoglycans.

David G

The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1993 ; 7 (11) : 1023-1030.

PMID 8370471

Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.

Hughes-Benzie RM, Pilia G, Xuan JY, Hunter AG, Chen E, Golabi M, Hurst JA, Kobori J, Marymee K, Pagon RA, Punnett HH, Schelley S, Tolmie JL, Wohlferd MM, Grossman T, Schlessinger D, MacKenzie AE

American journal of medical genetics. 1996 ; 66 (2) : 227-234.

PMID 8958336

Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.

Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D

Nature genetics. 1996 ; 12 (3) : 241-247.

PMID 8589713

Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes.

Eggenschwiler J, Ludwig T, Fisher P, Leighton PA, Tilghman SM, Efstratiadis A

Genes & development. 1997 ; 11 (23) : 3128-3142.

PMID 9389646

Isolation of a cDNA corresponding to a developmentally regulated transcript in rat intestine.

Filmus J, Church JG, Buick RN

Molecular and cellular biology. 1988 ; 8 (10) : 4243-4249.

PMID 3185547

A patient with Simpson-Golabi-Behmel syndrome and hepatocellular carcinoma.

Lapunzina P, Badia I, Galoppo C, De Matteo E, Silberman P, Tello A, Grichener J, Hughes-Benzie R

Journal of medical genetics. 1998 ; 35 (2) : 153-156.

PMID 9507397

Molecular genetics of Wiedemann-Beckwith syndrome.

Li M, Squire JA, Weksberg R

American journal of medical genetics. 1998 ; 79 (4) : 253-259.

PMID 9781904

Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome.

Neri G, Gurrieri F, Zanni G, Lin A

American journal of medical genetics. 1998 ; 79 (4) : 279-283.

PMID 9781908

Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome.

Pellegrini M, Pilia G, Pantano S, Lucchini F, Uda M, Fumi M, Cao A, Schlessinger D, Forabosco A

Developmental dynamics : an official publication of the American Association of Anatomists. 1998 ; 213 (4) : 431-439.

PMID 9853964

Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome.

Brzustowicz LM, Farrell S, Khan MB, Weksberg R

American journal of human genetics. 1999 ; 65 (3) : 779-783.

PMID 10441586

Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma.

Murthy SS, Shen T, De Rienzo A, Lee WC, Ferriola PC, Jhanwar SC, Mossman BT, Filmus J, Testa JR

Oncogene. 2000 ; 19 (3) : 410-416.

PMID 10656689

glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development.

Paine-Saunders S, Viviano BL, Zupicich J, Skarnes WC, Saunders S

Developmental biology. 2000 ; 225 (1) : 179-187.

PMID 10964473

Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions.

Tumova S, Woods A, Couchman JR

The international journal of biochemistry & cell biology. 2000 ; 32 (3) : 269-288.

PMID 10716625

Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition.

DeBaun MR, Ess J, Saunders S

Molecular genetics and metabolism. 2001 ; 72 (4) : 279-286.

PMID 11286501

Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis.

Grisaru S, Cano-Gauci D, Tee J, Filmus J, Rosenblum ND

Developmental biology. 2001 ; 231 (1) : 31-46.

PMID 11180950

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Contributor(s)

Written	09-2000	Hope H Punnett
		Genetics Laboratory, St. Christopher's Hospital for Children, Erie Avenue at Front Street, Philadelphia, PA 19134, USA
Updated	05-2002	Daniel Sinnett

Citation

This paper should be referenced as such :

Punnett HH . Simpson-Golabi-Behmel Syndrome. Atlas Genet Cytogenet Oncol Haematol. Septem ber 2000 . URL : http://AtlasGeneticsOncology.org/Genes/SimpsonGolabiID10038.html

Sinnett D . Simpson-Golabi-Behmel Syndrome. Atlas Genet Cytogenet Oncol Haematol. May 2002 . URL : http://AtlasGeneticsOncology.org/Genes/SimpsonGolabiID10038.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Sep 24 21:08:25 2008

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