CAKUT

Gene: CENPF

Kept rating as Amber following agreement from Helen Brittain, Genomics England Clinical Team: the evidence for a congenital renal anomaly is borderline, and in view of two families only, Amber is appropriate until further families are identified.

Created: 21 Apr 2020, 3:23 p.m. | Last Modified: 21 Apr 2020, 3:23 p.m.

Panel Version: 1.58

Comment on list classification: Updated rating from Grey to Amber. Gene was added to panel and rated Green by Zornitza Stark. Although CENPF has 'probable' disease confidence in Gene2Phenotype for Stromme syndrome, there are sufficient cases in OMIM and the literature to support the gene:disease association. Hydronephrosis/renal hypoplasia is seen in at least 2 Stromme families, but the phenotype is variable. CENPF is Green on the 'Renal ciliopathies' panel (Panel #725, V1.12). Rated as Amber awaiting further clinical feedback.

Created: 31 Mar 2020, 1:06 p.m. | Last Modified: 31 Mar 2020, 1:06 p.m.

Panel Version: 1.53

PMID:26820108 (Filges et al., 2016) describe long-term clinical follow up for siblings reported by Stromme et al. (1993) with intestingal atresia, ocular anomalis and microcephaly. They detect truncating compound het variants in CENPF in the original family (Family A) and an additional sibling pair (Family B). The original siblings (Family A) had normal renal newborn ultrasounds. The additional siblings (Family B) had Hydronephrosis/bilateral renal hypoplasia in addition to Duodenal atresia and other gastrointestinal phenotypes.

Created: 31 Mar 2020, 10:55 a.m. | Last Modified: 31 Mar 2020, 10:55 a.m.

Panel Version: 1.52

PMID:25564561 (Waters et al., 2015) ientified a non-consagnuineous Caucasian kindred with 4 affected fetuses. Autopsy revealed phenotypes including Duodenal atresia and Bilateral renal hypolasia.

Created: 31 Mar 2020, 10:55 a.m. | Last Modified: 31 Mar 2020, 10:55 a.m.

Panel Version: 1.52

PMID:28407396 (Ozkinay et al., 2017) report a Stromme syndrome family with 2 affected individuals and a homozygous p.T1974Nfs*9 variant in CENPF. Renal phenotypes are not recorded in table 1.

Created: 31 Mar 2020, 10:54 a.m. | Last Modified: 31 Mar 2020, 10:54 a.m.

Panel Version: 1.52

PMID:31953238 (Alghamdi et al. 2020) report 2 young brothers with Stromme syndrome and a c.1195-2A>G CENPF variant, one of whom died age 3 months. The full text is unavailable but a renal phenotype is not recorded in the abstract.

Created: 31 Mar 2020, 10:54 a.m. | Last Modified: 31 Mar 2020, 10:54 a.m.

Panel Version: 1.52

Green List (high evidence)

Renal hypodysplasia and hydronephrosis are a feature of this syndrome.
Sources: Expert list

Created: 16 Jan 2020, 3:22 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Stromme syndrome, MIM#243605