Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus.

Article Details


Mitchell K, O'Sullivan J, Missero C, Blair E, Richardson R, Anderson B, Antonini D, Murray JC, Shanske AL, Schutte BC, Romano RA, Sinha S, Bhaskar SS, Black GC, Dixon J, Dixon MJ

Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus.

Am J Hum Genet. 2012 Jan 13;90(1):69-75. doi: 10.1016/j.ajhg.2011.11.013. Epub 2011 Dec 22.

PubMed ID
22197488 [ View in PubMed

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.

DrugBank Data that Cites this Article

NameUniProt ID
Receptor-interacting serine/threonine-protein kinase 4P57078Details