Universität zu Köln

Gollasch, Benjamin, Basmanav, Fitnat Buket, Nanda, Arti ORCID: 0000-0002-1223-3181, Fritz, Guenter ORCID: 0000-0002-4571-8812, Mahmoudi, Hassnaa, Thiele, Holger, Wehner, Maria, Wolf, Sabrina, Altmueller, Janine, Nuernberg, Peter, Frank, Jorge and Betz, Regina C. (2015). Identification of a novel mutation in RIPK4 in a kindred with phenotypic features of Bartsocas-Papas and CHAND syndromes. Am. J. Med. Genet. A, 167 (11). S. 2555 - 2563. HOBOKEN: WILEY. ISSN 1552-4833

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Abstract

Three children from an expanded consanguineous Kuwaiti kindred presented with ankyloblepharon, sparse and curly hair, and hypoplastic nails, suggestive of CHAND syndrome (OMIM 214350) that belongs to the heterogeneous spectrum of ectodermal dysplasias. After exclusion of pathogenic mutations in TP63 we performed homozygosity mapping, followed by exome sequencing of one affected individual. We initially identified three homozygous mutations in the linked region, located in PWP2, MX2 and RIPK4. Recently, mutations in RIPK4 have been reported in Bartsocas-Papas syndrome (OMIM 263650) that shows overlapping clinical symptoms with the phenotype observed in the affected individuals studied here. Subsequent analysis of affected and non-affected family members showed that mutation c.850G>A (p.Glu284Lys) in RIPK4 was in complete segregation with the disease phenotype, in accordance with an autosomal recessive inheritance pattern, thus supporting pathogenicity of this variant. Interestingly, however, our patients did not have cleft lip/palate, a common feature encountered in Bartsocas-Papas syndrome. Whereas in Bartsocas-Papas syndromes missense mutations are usually located within the serin/threonin kinase of RIPK4, the mutation detected in our family resides just outside of the kinase domain, which could explain the milder phenotype. Our data raise the question if CHAND syndrome indeed is a distinct entity. Alternatively, CHAND and Bartsocas-Papas syndrome might be allelic disorders or RIPK4 mutations could confer varying degrees of phenotypic severity, depending on their localization within or outside functionally important domains. Our findings indicate that making an accurate diagnosis based only on the prevailing clinical symptoms is challenging. (c) 2015 Wiley Periodicals, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gollasch, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Basmanav, Fitnat Buket UNSPECIFIED UNSPECIFIED UNSPECIFIED Nanda, Arti UNSPECIFIED orcid.org/0000-0002-1223-3181 UNSPECIFIED Fritz, Guenter UNSPECIFIED orcid.org/0000-0002-4571-8812 UNSPECIFIED Mahmoudi, Hassnaa UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Wehner, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Jorge UNSPECIFIED UNSPECIFIED UNSPECIFIED Betz, Regina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-388368
DOI:	10.1002/ajmg.a.37233
Journal or Publication Title:	Am. J. Med. Genet. A
Volume:	167
Number:	11
Page Range:	S. 2555 - 2563
Date:	2015
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1552-4833
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REGULATORY FACTOR 6; IKK-ALPHA; MICE LACKING; PROTEIN; ACTIVATION; IRF6; AEC; P63; DIFFERENTIATION; PATHOGENESIS Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38836