CAKUT

Gene: DHCR7

Comment on list classification: Updated rating from Amber to Green on advice from Helen Brittain (Genomics England Clinical Team). Helen notes that it meets the inclusion criteria (renal malformations as part of a wider syndromic phenotype). There are other post-natally relevant renal malformations (unilateral agenesis, hydronephrosis and cysts). It is also a gene that we have a biochemical test for, so VUSs would be easier to re-categorise than some genes.

Created: 18 May 2020, 8:16 a.m. | Last Modified: 18 May 2020, 8:16 a.m.

Panel Version: 1.112

Comment on list classification: Added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Amber. Renal phenotypes are only seen in approximately 25% of SLOS patients, and renal anomalies are more commonly detected prenatally than postnatally (PMID:23059950) so DHCR7 is more appropriate for the Fetal anomalies panel.

Created: 30 Apr 2020, 4:03 p.m. | Last Modified: 30 Apr 2020, 4:04 p.m.

Panel Version: 1.73

PMID:9678700. Ryan et al., 1998 reviewed all known UK cases of SLOS. Half had been terminated or died in infancy. 14 (29%) had structural renal abnormalities.

Created: 30 Apr 2020, 4:02 p.m. | Last Modified: 30 Apr 2020, 4:02 p.m.

Panel Version: 1.71

PMID:23059950. Nowaczyk and Irons, 2012 note that approximately 25% of affected individuals have renal anomalies (most common being renal hypoplasia or agenesis, renal cortical cysts, hydronephrosis and structural anomalies of the collecting system). They also note that renal anomalies are amongst the phenotypes seen more commonly prenatally than postnatally.

Created: 30 Apr 2020, 4:02 p.m. | Last Modified: 30 Apr 2020, 4:02 p.m.

Panel Version: 1.71

PMID:10069707. Kratz and Kelley, 1999 report on prenatal diagnosis of SLOS. Fetal phenotypes included renal agenesis, renal pyelectasis, hydronephrosis (4 patients)

Created: 30 Apr 2020, 4:02 p.m. | Last Modified: 30 Apr 2020, 4:02 p.m.

Panel Version: 1.71

PMID:31840946 (Schoner et al., 2020) performed autopsies and DHCR7 gene analyses in 8 fetuses suspected of having SLOS. 5/9 fetuses presented with classic SLOS features including renal anomalies. DHCR7 variants were confirmed in cases 1-5 and 7.

Created: 30 Apr 2020, 3:30 p.m. | Last Modified: 30 Apr 2020, 3:30 p.m.

Panel Version: 1.69

Green List (high evidence)

Approximately 25% of affected individuals have renal anomalies, most commonly renal hypoplasia or agenesis, renal cortical cysts, hydronephrosis, and structural anomalies of the collecting system [Curry et al 1987, Ryan et al 1998, Kratz & Kelley 1999, Nowaczyk et al 2001].
Sources: Expert list

Created: 16 Jan 2020, 3:43 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Smith-Lemli-Opitz syndrome, MIM# 270400

Publications

• 3812577
• 10069707
• 23059950
• 9678700

Variants in this GENE are reported as part of current diagnostic practice