WDR35 variants in a cranioectodermal dysplasia patient with early onset end-stage renal disease and retinal dystrophy.

Cranioectodermal dysplasia (CED) is rare heterogeneous condition. It belongs to a group of disorders defined as ciliopathies and is associated with defective cilia function and structure. To date six genes have been associated with CED. Here we describe a 4-year-old male CED patient whose features include dolichocephaly, multi-suture craniosynostosis, epicanthus, frontal bossing, narrow thorax, limb shortening, and brachydactyly. The patient presented early-onset chronic kidney disease and was transplanted at the age of 2 years and 5 months. At the age of 3.5 years a retinal degeneration was diagnosed. Targeted sequencing by NGS revealed the presence of compound heterozygous variants in the WDR35 gene. The variants are a novel missense change in exon 9 p.(Gly303Arg) and a previously described nonsense variant in exon 18 p.(Leu641*). Our findings suggest that patients with WDR35 defects may be at risk to develop early-onset retinal degeneration. Therefore, CED patients with pathogenic variation in this gene should be assessed at least once by the ophthalmologist before the age of 4 years to detect early signs of retinal degeneration.

[Apoptosis--molecular basis in pathogenesis of selected chronic inflammatory and neoplastic diseases]. / Apoptoza--podloze molekularne patogenezy wybranych przewleklych procesów zapalnych i nowotworowych.

Apoptosis is a physiological programmed cell death. The molecular regulation of this process is very complex and still unknown. Disregulation in the mechanisms controlling apoptosis are thought to be the cause of many diseases. Mutations in gene p53 lead to carcinous transformation, high expression of receptor Fas increases the cell elimination in chronic inflammatory processes. Wrong balance between apoptosis regulatory proteins Bcl-2/Bax is the reason for low mortality, radioresistance and chemoresistance. Studies of mechanisms controlling interactions between apoptotic proteins will let us find new diagnostic and therapeutic methods.