Mutations in WDR19 encoding the intraflagellar transport component IFT144 cause a broad spectrum of ciliopathies
Fehrenbach H, Decker C, Eisenberger T, Frank V, Hampel T, Walden U, Amann KU, Krueger-Stollfuss I, Bolz HJ, Haeffner K, Pohl M, Bergmann C (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: Springer Verlag (Germany)
Book Volume: 29
Pages Range: 1451-6
Journal Issue: 8
DOI: 10.1007/s00467-014-2762-2
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.
Authors with CRIS profile
Involved external institutions
Klinikum Memmingen
Germany (DE)
Bioscientia Healthcare Group
Germany (DE)
Klinikum Augsburg
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Universitätsklinikum Freiburg
Germany (DE)
Germany (DE)
Bioscientia Healthcare Group
Germany (DE)
Klinikum Augsburg
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Universitätsklinikum Freiburg
Germany (DE)
How to cite
APA:
Fehrenbach, H., Decker, C., Eisenberger, T., Frank, V., Hampel, T., Walden, U.,... Bergmann, C. (2014). Mutations in WDR19 encoding the intraflagellar transport component IFT144 cause a broad spectrum of ciliopathies. Pediatric Nephrology, 29(8), 1451-6. https://doi.org/10.1007/s00467-014-2762-2
MLA:
Fehrenbach, Henry, et al. "Mutations in WDR19 encoding the intraflagellar transport component IFT144 cause a broad spectrum of ciliopathies." Pediatric Nephrology 29.8 (2014): 1451-6.
BibTeX: Download