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PMID: 20436468 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.

Nature genetics ·Vol. 42 ·No. 6 ·2010-06-00 ·Pages 483-5

Hoischen A, van Bon BW, Gilissen C, Arts P, van Lier B, Steehouwer M, de Vries P, de Reuver R, Wieskamp N, Mortier G, Devriendt K, Amorim MZ, Revencu N, Kidd A, Barbosa M, Turner A, Smith J, Oley C, Henderson A, Hayes IM, Thompson EM, Brunner HG, de Vries BB, Veltman JA

Abstract

Schinzel-Giedion syndrome is characterized by severe mental retardation, distinctive facial features and multiple congenital malformations; most affected individuals die before the age of ten. We sequenced the exomes of four affected individuals (cases) and found heterozygous de novo variants in SETBP1 in all four. We also identified SETBP1 mutations in eight additional cases using Sanger sequencing. All mutations clustered to a highly conserved 11-bp exonic region, suggesting a dominant-negative or gain-of-function effect.

MeSH Terms

Abnormalities, Multiple/genetics Base Sequence Carrier Proteins/genetics Face/abnormalities Humans Intellectual Disability/genetics Molecular Sequence Data Mutation Nuclear Proteins/genetics Syndrome

Chemicals

Carrier Proteins Nuclear Proteins SETBP1 protein, human

Authors & Affiliations

24 authors, click to expand affiliations / ORCID

Hoischen Alexander

Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

van Bon Bregje W M

Gilissen Christian

Arts Peer

van Lier Bart

Steehouwer Marloes

de Vries Petra

de Reuver Rick

Wieskamp Nienke

Mortier Geert

Devriendt Koen

Amorim Marta Z

Revencu Nicole

Kidd Alexa

Barbosa Mafalda

Turner Anne

Smith Janine

Oley Christina

Henderson Alex

Hayes Ian M

Thompson Elizabeth M

Brunner Han G

de Vries Bert B A

Veltman Joris A

References (15)

15 references, click to expand

Chick cartilage chondroitin sulfate proteoglycan core protein. I. Generation and characterization of peptides and specificity for glycosaminoglycan attachment.
J Biol Chem. 1990 Jul 15;265(20):12075-87 PMID: 2365711
Targeted capture and massively parallel sequencing of 12 human exomes.
Nature. 2009 Sep 10;461(7261):272-6 PMID: 19684571
Further clinical and sensorial delineation of Schinzel-Giedion syndrome: report of two cases.
Am J Med Genet. 2002 May 1;109(3):211-7 PMID: 11977181
Massively parallel sequencing of ataxia genes after array-based enrichment.
Hum Mutat. 2010 Apr;31(4):494-9 PMID: 20151403
Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET.
Eur J Biochem. 2001 Mar;268(5):1340-51 PMID: 11231286
A syndrome of severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations in sibs.
Am J Med Genet. 1978;1(4):361-75 PMID: 665725
A gene atlas of the mouse and human protein-encoding transcriptomes.
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7 PMID: 15075390
Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.
Nat Genet. 2004 Sep;36(9):955-7 PMID: 15300250
Noonan syndrome and related disorders: genetics and pathogenesis.
Annu Rev Genomics Hum Genet. 2005;6:45-68 PMID: 16124853
Schinzel-Giedion syndrome: report of splenopancreatic fusion and proposed diagnostic criteria.
Am J Med Genet A. 2008 May 15;146A(10):1299-306 PMID: 18398855
Delineation of a critical region on chromosome 18 for the del(18)(q12.2q21.1) syndrome.
Am J Med Genet A. 2008 May 15;146A(10):1330-4 PMID: 18412119
Exome sequencing identifies the cause of a mendelian disorder.
Nat Genet. 2010 Jan;42(1):30-5 PMID: 19915526
SET-domain proteins of the Su(var)3-9, E(z) and trithorax families.
Gene. 2002 Feb 20;285(1-2):25-37 PMID: 12039029
There are two major types of skeletal keratan sulphates.
Biochem J. 1990 Oct 1;271(1):243-5 PMID: 2222415
Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12).
Br J Haematol. 2007 Jan;136(2):294-6 PMID: 17233820

Article Info

Journal

Nature genetics

Abbr.

Nat Genet

ISSN

1546-1718

DOI

10.1038/ng.581

Published

2010-06-00

Epub

2010-00-02

Pages

483-5

Language

English

Region

United States

NLM ID

9216904

Subset

Corrections

CommentIn

PMID: 20718797

External Links

PubMed source DOI: 10.1038/ng.581 View journal details

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De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.

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