@article {611,
	title = {Mutations in WDR4 as a new cause of Galloway-Mowat syndrome.},
	journal = {Am J Med Genet A},
	volume = {176},
	year = {2018},
	month = {2018 Nov},
	pages = {2460-2465},
	abstract = {<p>Galloway-Mowat syndrome (GAMOS) is a phenotypically heterogeneous disorder characterized by neurodevelopmental defects combined with renal-glomerular disease, manifesting with proteinuria. To identify additional monogenic disease causes, we here performed whole exome sequencing (WES), linkage analysis, and homozygosity mapping in three affected siblings of an Indian family with GAMOS. Applying established criteria for variant filtering, we identify a novel homozygous splice site mutation in the gene WDR4 as the likely disease-causing mutation in this family. In line with previous reports, we observe growth deficiency, microcephaly, developmental delay, and intellectual disability as phenotypic features resulting from WDR4 mutations. However, the newly identified allele additionally gives rise to proteinuria and nephrotic syndrome, a phenotype that was never reported in patients with WDR4 mutations. Our data thus expand the phenotypic spectrum of WDR4 mutations by demonstrating that, depending on the specific mutated allele, a renal phenotype may be present. This finding suggests that GAMOS may occupy a phenotypic spectrum with other microcephalic diseases. Furthermore, WDR4 is an additional example of a gene that encodes a tRNA modifying enzyme and gives rise to GAMOS, if mutated. Our findings thereby support the recent observation that, like neurons, podocytes of the renal glomerulus are particularly vulnerable to cellular defects resulting from altered tRNA modifications.</p>},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.40489},
	author = {Braun, Daniela A and Shril, Shirlee and Sinha, Aditi and Schneider, Ronen and Tan, Weizhen and Ashraf, Shazia and Hermle, Tobias and Jobst-Schwan, Tilman and Widmeier, Eugen and Majmundar, Amar J and Daga, Ankana and Warejko, Jillian K and Nakayama, Makiko and Schapiro, David and Chen, Jing and Airik, Merlin and Rao, Jia and Schmidt, Johanna Magdalena and Hoogstraten, Charlotte A and Hugo, Hannah and Meena, Jitendra and Lek, Monkol and Laricchia, Kristen M and Bagga, Arvind and Hildebrandt, Friedhelm}
}
