Newborns main panel

Gene: CTNS

Special Consideration: Awareness.

Additional Information: a 57kb deletion is a common pathogenic variant.

Created: 25 Sep 2024, 4:13 p.m. | Last Modified: 25 Sep 2024, 4:13 p.m.

Panel Version: 0.469

The mechanism of pathogenicity is loss-of-function (LOF).

Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.

Panel Version: 0.137

CTNS mutations in patients with cystinosis - PubMed (nih.gov)

Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.

Panel Version: 0.134

There are 4 subtypes of cystinosis phenotype, all autosomal recessive, and all included in newborns. MOP is LOF, and there are truncating variants as well as missense variants associated, where truncating are usually more severe and missense less severe. There are also some intronic/splicing variants. There are some genotype-phenotype correlations (GeneReviews has extensive section on this). Summary: Biallelic truncating variants (also a 57kb deletion) are associated with the more severe earlier-onset phenoytpes; whereas milder missense variants are associated with milder and later-onset phenotypes. Individuals with one truncating (severe) variant and one mild variant usually present with intermediate phenotype. Deletions of CTNS and its flanking genes may lead to contiguous gene deletion syndromes with more complex phenotypes than those of classic cystinosis. For example, the 57-kb deletion on chromosome 17p13 extends into TRPV1 causing dysregulation of TRPV1 transcription in peripheral blood mononuclear cells.

Created: 10 Mar 2023, 11:03 a.m. | Last Modified: 10 Mar 2023, 11:03 a.m.

Panel Version: 0.41