Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic

Gene: CHD1L

Comment when marking as ready: The population variant frequencies are out of keeping for a Mendelian disorder.

Created: 18 Jun 2020, 10:36 a.m. | Last Modified: 18 Jun 2020, 10:36 a.m.

Panel Version: 0.72

I don't know

Review of this gene during variant curation. The 6 missense variants reported in the two papers (PMID: 22146311, 24429398) are very common in gnomAD:
CHD1L:c.2098G>A; p.Gly700Arg - 1110 hets, 5 hom
CHD1L:c.2295A>G; p.Ile765Met - 468 hets, 1 hom
CHD1L:c.2479A>G; p.Ile827Val – 725 hets, 2 hom
CHD1L:c.998C>G; p.Pro333Arg – 1 het, 0 hom
CHD1L:c.1199A>G; p.Glu400Gly – 3 hets, 0 hom
CHD1L:c.1551A>G; p.Ile517Met – 195 hets, 0 hom
I could not find any other papers for this gene in association with CAKUT. ClinVar only has 1 frameshift variant reported as pathogenic from research in 2001 for an unrelated condition (short stature), the other variants reported in this gene are VUS or LB/B.

Created: 18 Jun 2020, 3:48 a.m. | Last Modified: 18 Jun 2020, 3:48 a.m.

Panel Version: 0.71

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
CAKUT

Publications

• 22146311, 24429398

Green List (high evidence)

Two of three novel heterozygous missense variants identified in 3 CAKUT patients. Quantitative messenger RNA analysis demonstrated high CHD1L expression in human fetal kidneys, and levels were four times higher than in adult kidneys. In the human embryo at 7-11 weeks gestation, CHD1L immunolocalized in the early ureteric bud and the S- and comma-shaped bodies, critical stages of kidney development. In normal postnatal sections, CHD1L was expressed in the cytoplasm of tubular cells in all tubule segments. CHD1L expression appeared higher in the hydronephrotic kidney of one patient with a hypofunctional CHD1L variant than in normal kidneys, recapitulating high fetal levels.

5 unrelated patients with CAKUT and CHD1L

Created: 16 Jan 2020, 3:31 a.m. | Last Modified: 16 Jan 2020, 3:31 a.m.

Panel Version: 0.27

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
CAKUT

Publications

• PMID: 22146311, 24429398