Universität zu Köln

Fehrenbach, Henry, Decker, Christian, Eisenberger, Tobias, Frank, Valeska, Hampel, Tobias, Walden, Ulrike, Amann, Kerstin U., Krueger-Stollfuss, Ingrid, Bolz, Hanno J., Haeffner, Karsten, Pohl, Martin and Bergmann, Carsten (2014). Mutations in WDR19 encoding the intraflagellar transport component IFT144 cause a broad spectrum of ciliopathies. Pediatr. Nephrol., 29 (8). S. 1451 - 1457. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

An emerging number of clinically and genetically heterogeneous diseases now collectively termed ciliopathies have been connected to the dysfunction of primary cilia. We describe an 8-year-old girl with a complex phenotype that did not clearly match any familiar syndrome. Hypotonia, facial dysmorphism and retardation were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Renal biopsy revealed tubular atrophy, interstitial fibrosis and segmental glomerulosclerosis. After exclusion of a chromosomal abnormality by array-comparative genomic hybridization (CGH), we performed next-generation sequencing (NGS) using a customized panel that targeted 131 genes known or hypothesized to cause ciliopathies. We identified the novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) that affects an evolutionarily highly conserved residue in the intraflagellar transport protein IFT144, is absent from databases and is predicted to be pathogenic by all bioinformatic sources used. Mutations in WDR19 encoding the intraflagellar transport component IFT144 have recently been described in single families with the clinically overlapping skeletal ciliopathies Jeune and Sensenbrenner syndromes, combined or isolated nephronophthisis (NPHP) and retinitis pigmentosa (RP) (Senior-Loken syndrome). Our patient emphasizes the usefulness and efficiency of a comprehensive NGS panel approach in patients with unclassified ciliopathies. It further suggests that WDR19 mutations can cause a broad spectrum of ciliopathies that extends to Jeune and Sensenbrenner syndromes, RP and renal NPHP-like phenotypes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fehrenbach, Henry UNSPECIFIED UNSPECIFIED UNSPECIFIED Decker, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Eisenberger, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Valeska UNSPECIFIED UNSPECIFIED UNSPECIFIED Hampel, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Walden, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Amann, Kerstin U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger-Stollfuss, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haeffner, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Pohl, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-433442
DOI:	10.1007/s00467-014-2762-2
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	29
Number:	8
Page Range:	S. 1451 - 1457
Date:	2014
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-198X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DISEASE Multiple languages Pediatrics; Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43344