Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus

Karen Mitchell; James O'Sullivan; Caterina Missero; Ed Blair; Rose Richardson; Beverley Anderson; Dario Antonini; Jeffrey C Murray; Alan L Shanske; Brian C Schutte; Rose-Anne Romano; Satrajit Sinha; Sanjeev S Bhaskar; Graeme C M Black; Jill Dixon; Michael J Dixon

doi:10.1016/j.ajhg.2011.11.013

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Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus

Journal article

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Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus

Karen Mitchell, James O'Sullivan, Caterina Missero, Ed Blair, Rose Richardson, Beverley Anderson, Dario Antonini, Jeffrey C Murray, Alan L Shanske, Brian C Schutte, …

American journal of human genetics, Vol.90(1), pp.69-75

01/13/2012

DOI: 10.1016/j.ajhg.2011.11.013

PMCID: PMC3257958

PMID: 22197488

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Abstract

Pterygium syndromes are complex congenital disorders that encompass several distinct clinical conditions characterized by multiple skin webs affecting the flexural surfaces often accompanied by craniofacial anomalies. In severe forms, such as in the autosomal-recessive Bartsocas-Papas syndrome, early lethality is common, complicating the identification of causative mutations. Using exome sequencing in a consanguineous family, we identified the homozygous mutation c.1127C>A in exon 7 of RIPK4 that resulted in the introduction of the nonsense mutation p.Ser376X into the encoded ankyrin repeat-containing kinase, a protein that is essential for keratinocyte differentiation. Subsequently, we identified a second mutation in exon 2 of RIPK4 (c.242T>A) that resulted in the missense variant p.Ile81Asn in the kinase domain of the protein. We have further demonstrated that RIPK4 is a direct transcriptional target of the protein p63, a master regulator of stratified epithelial development, which acts as a nodal point in the cascade of molecular events that prevent pterygium syndromes.

Mutation

Cleft Palate - diagnosis

Skin Abnormalities

Cleft Lip - diagnosis

Exons

Humans

Molecular Sequence Data

Male

Cleft Palate - genetics

Genetic Loci

Phosphoproteins - metabolism

Pterygium - genetics

Exome

Base Sequence

Child

Craniofacial Abnormalities - genetics

Severity of Illness Index

Amino Acid Sequence

Tumor Suppressor Proteins - metabolism

Protein-Serine-Threonine Kinases - genetics

Genes, Recessive

Transcription Factors - metabolism

Cleft Lip - genetics

Animals

Keratinocytes - metabolism

Trans-Activators - metabolism

Consanguinity

Mice

Pterygium - congenital

Pterygium - diagnosis

Details

Title: Subtitle: Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus
Creators: Karen Mitchell - Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, UK
James O'Sullivan
Caterina Missero
Ed Blair
Rose Richardson
Beverley Anderson
Dario Antonini
Jeffrey C Murray
Alan L Shanske
Brian C Schutte
Rose-Anne Romano
Satrajit Sinha
Sanjeev S Bhaskar
Graeme C M Black
Jill Dixon
Michael J Dixon
Resource Type: Journal article
Publication Details: American journal of human genetics, Vol.90(1), pp.69-75
DOI: 10.1016/j.ajhg.2011.11.013
PMID: 22197488
PMCID: PMC3257958
NLM abbreviation: Am J Hum Genet
ISSN: 0002-9297
eISSN: 1537-6605
Publisher: United States
Grant note: GGP09230 / Telethon R01 DE008559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS DE13513 / NIDCR NIH HHS G0901539 / Medical Research Council DE08559 / NIDCR NIH HHS R01 DE013513 / NIDCR NIH HHS
Language: English
Date published: 01/13/2012
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025357902771

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