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PMID: 20817137 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.

American journal of human genetics ·Vol. 87 ·No. 3 ·2010-09-10 ·Pages 418-23

Gilissen C, Arts HH, Hoischen A, Spruijt L, Mans DA, Arts P, van Lier B, Steehouwer M, van Reeuwijk J, Kant SG, Roepman R, Knoers NV, Veltman JA, Brunner HG

Abstract

Sensenbrenner syndrome/cranioectodermal dysplasia (CED) is an autosomal-recessive disease that is characterized by craniosynostosis and ectodermal and skeletal abnormalities. We sequenced the exomes of two unrelated CED patients and identified compound heterozygous mutations in WDR35 as the cause of the disease in each of the two patients independently, showing that it is possible to find the causative gene by sequencing the exome of a single sporadic patient. With RT-PCR, we demonstrate that a splice-site mutation in exon 2 of WDR35 alters splicing of RNA on the affected allele, introducing a premature stop codon. WDR35 is homologous to TULP4 (from the Tubby superfamily) and has previously been characterized as an intraflagellar transport component, confirming that Sensenbrenner syndrome is a ciliary disorder.

MeSH Terms

Abnormalities, Multiple/genetics Apoptosis Regulatory Proteins/genetics Base Sequence Child DNA Mutational Analysis Ectodermal Dysplasia/genetics Exons/genetics Humans Membrane Proteins/genetics Molecular Sequence Data Mutation/genetics RNA Splice Sites/genetics Sequence Analysis, DNA/methods Syndrome

Chemicals

Apoptosis Regulatory Proteins Membrane Proteins RNA Splice Sites naofen protein, human

Authors & Affiliations

14 authors, click to expand affiliations / ORCID

Gilissen Christian

Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, The Netherlands.

Arts Heleen H

Hoischen Alexander

Spruijt Liesbeth

Mans Dorus A

Arts Peer

van Lier Bart

Steehouwer Marloes

van Reeuwijk Jeroen

Kant Sarina G

Roepman Ronald

Knoers Nine V A M

Veltman Joris A

Brunner Han G

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Article Info

Journal

American journal of human genetics

Abbr.

Am J Hum Genet

ISSN

1537-6605

DOI

10.1016/j.ajhg.2010.08.004

Published

2010-09-10

Pages

418-23

Language

English

Region

United States

NLM ID

0370475

PMCID

PMC2933349

Subset

External Links

PubMed source DOI: 10.1016/j.ajhg.2010.08.004 PMC Full Text View journal details

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Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.

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