Exome Sequence Identifies RIPK4 As the Bartsocas-Papas Syndrome Locus

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2011 Dec 27

PMID 22197488

Citations 47

Authors

Karen Mitchell

James OSullivan

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

Affiliations

Soon will be listed here.

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.

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