CAKUT

Gene: DHCR7

Green List (high evidence)

DHCR7 (7-dehydrocholesterol reductase)
EnsemblGeneIds (GRCh38): ENSG00000172893
EnsemblGeneIds (GRCh37): ENSG00000172893
OMIM: 602858, Gene2Phenotype
DHCR7 is in 29 panels

2 reviews

Rebecca Foulger (Genomics England curator)

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

Zornitza Stark (Australian Genomics)

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

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

History Filter Activity

18 May 2020, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: dhcr7 has been classified as Green List (High Evidence).

30 Apr 2020, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: dhcr7 has been classified as Amber List (Moderate Evidence).

30 Apr 2020, Gel status: 0

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: dhcr7 has been removed from the panel.

30 Apr 2020, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: DHCR7 were changed from Smith-Lemli-Opitz syndrome, MIM# 270400 to Smith-Lemli-Opitz syndrome, 270400; renal agenesis

30 Apr 2020, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: DHCR7 were set to 3812577; 10069707; 23059950; 9678700

16 Jan 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: DHCR7 was added gene: DHCR7 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DHCR7 were set to 3812577; 10069707; 23059950; 9678700 Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM# 270400 gene: DHCR7 was marked as current diagnostic