Proteinuric renal disease

Gene: DKC1

Red List (low evidence)

Comment on list classification: Promoting this gene from grey to red as there is one reported family with a missense variant in this gene and a phenotype that includes nephrotic syndrome.

Created: 13 Jan 2021, 5:43 p.m. | Last Modified: 13 Jan 2021, 5:43 p.m.

Panel Version: 2.34

Variants in this gene have previously been associated with dyskeratosis congenita (bone marrow failure) characterized by telomere attrition. https://omim.org/entry/300126

As reported by expert reviewer PMID: 32554502 - Balogh et al 2020 - reports a large pedigree in which 6 affected males presented with an infantile-onset disorder characterized by steroid-resistant nephrotic syndrome, cataracts (prior to steroid treatment), sensorineural deafness, and enterocolitis and died in early childhood. Using linkage analysis they identified a point mutation in DKC1 (c.616 G>A, p.Glu206Lys) that segregated with the disease in generation II. The variant is absent from gnomAD. An affected female was found to have skewed x-inactivation.

Created: 13 Jan 2021, 5:40 p.m. | Last Modified: 13 Jan 2021, 5:50 p.m.

Panel Version: 2.34

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Publications

• 32554502

Red List (low evidence)

six affected males in one pedigree
Sources: Literature

Created: 18 Nov 2020, 11:01 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
steroid-resistant 6 nephrotic syndrome; cataracts (prior to steroid treatment); sensorineural deafness; enterocolitis

Publications

• 32554502