Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

NEK1 mutations cause short-rib polydactyly syndrome type majewski.

Authors: Thiel, C  Kessler, K  Giessl, A  Dimmler, A  Shalev, SA  Von der Haar, S  Zenker, M  Zahnleiter, D  Stoss, H  Beinder, E  Abou Jamra, R  Ekici, AB  Schroder-Kress, N  Aigner, T  Kirchner, T  Reis, A  Brandstatter, JH  Rauch, A 
Citation: Thiel C, etal., Am J Hum Genet. 2011 Jan 7;88(1):106-14. doi: 10.1016/j.ajhg.2010.12.004.
Pubmed: (View Article at PubMed) PMID:21211617
DOI: Full-text: DOI:10.1016/j.ajhg.2010.12.004

Defects of ciliogenesis have been implicated in a wide range of human phenotypes and play a crucial role in signal transduction and cell-cycle coordination. We used homozygosity mapping in two families with autosomal-recessive short-rib polydactyly syndrome Majewski type to identify mutations in NEK1 as an underlying cause of this lethal osteochondrodysplasia. NEK1 encodes a serine/threonine kinase with proposed function in DNA double-strand repair, neuronal development, and coordination of cell-cycle-associated ciliogenesis. We found that absence of functional full-length NEK1 severely reduces cilia number and alters ciliar morphology in vivo. We further substantiate a proposed digenic diallelic inheritance of ciliopathies by the identification of heterozygous mutations in NEK1 and DYNC2H1 in an additional family. Notably, these findings not only increase the broad spectrum of ciliar disorders, but suggest a correlation between the degree of defective microtubule or centriole elongation and organization and the severity of the resulting phenotype.


Disease Annotations
Phenotype Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 11069733
Created: 2016-04-27
Species: All species
Last Modified: 2016-04-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.