Defects in the WDR35 gene are associated with various disorders collectively known as ciliopathies.
Ciliopathies are a heterogenous group of diseases that affect multiple systems within the body, and are caused by defects in cilia function and/or structure.
The WDR35 gene encodes for a WDR35 protein (also known as IFT121 protein), which belongs to the complex A of the intraflagellar transport machinery (IFT). IFT is evolutionary conserved process, which plays an essential role in cilia formation and function.
Cilia are organelles projecting from the surface of most of the cell types in the human body, and play a crucial role during development and postnatal life.
To date 39 variants in the WDR35 gene have been identified. These include 20 missense and 6 nonsense changes. Moreover, 7 splicing and 5 small deletions have been reported in the Human Gene Mutation Database (HGMD).
Two changes p.(Leu641*) in exon 18 and p.(Asp841Val) in exon 22 have been frequently identified in this gene.
Diagnosis is made based on characteristic clinical features and molecular genetic testing, usually in the first years of life.
Genetic screening is based on entire WDR35 gene analysis or NGS based techniques. These include gene-target testing (e.g. ciliopathies panel, skeletal disorders panel, craniosynostosis panel, nephrology panel), and exome sequencing (WES). In a reasonable clinical situation also whole genome sequencing (WGS) might be performed.
WDR35