CAKUT

Gene: CEP55

Comment on list classification: Updated rating from Grey to Green. Gene was added to the panel and rated Green by Zornitza Stark. 3 separate variants from 3 different ethnic groups (2 of the variants are likely Founder variants), plus zebrafish model. Most homozygous nonsense variants are embryonic lethal but PMID:28295209 report viable compound het missense variants.

Created: 31 Mar 2020, 4:01 p.m. | Last Modified: 31 Mar 2020, 4:01 p.m.

Panel Version: 1.58

PMID:32100459 (Barrie et al., 2020) describe 7 individuals from 5 families with biallelic CEP55 variants. This is the first reported case of missense variants in CEP55 (Previously only a prenatal lethal phenotype was reported due to homozygous CEP55 nonsense variants). The authors suggest that compound het cases with nonsense and missense CEP55 variants have a different viable phenotype. Homozgyosity for a splice variant in CEP55 is compatible with life. Renal abnormality was reported in Patient 3.

Created: 31 Mar 2020, 3:25 p.m. | Last Modified: 31 Mar 2020, 3:25 p.m.

Panel Version: 1.55

PMID:28295209. Bondeson et al report a Swedish couple with 2 affected male fetuses homozygous for CEP55 p.Arg86*. Although the phenotype differed between fetuses, both exhibited kidney phenotypes (including renal dysplaisa). Segregation analysis supported the gene:disease association, and Haplotype analysis suggested a founder effect.

Created: 31 Mar 2020, 3:25 p.m. | Last Modified: 31 Mar 2020, 3:25 p.m.

Panel Version: 1.55

PMID:28264986: Frosk et al, 2017 report a Dutch-German Mennonite family with 3 affected fetuses homozygous for CEP55 nonsense variant p.Ser425* presenting with MIM:236500 including renal dysplasia.

Created: 31 Mar 2020, 1:43 p.m. | Last Modified: 31 Mar 2020, 1:43 p.m.

Panel Version: 1.54

PMID:30622327 (Rawlins et al) report a novel homozygous founder frameshift variant(p.Ile172Asnfs*17) in CEP55 in 2 siblings presenting with a lethal fetal disorder including cystic dysplastic kidneys. The variant is present at low frequency in the Amish community.

Created: 31 Mar 2020, 1:43 p.m. | Last Modified: 31 Mar 2020, 1:43 p.m.

Panel Version: 1.54

Green List (high evidence)

Three families and a zebrafish model support gene-disease association.
Sources: Expert list

Created: 16 Jan 2020, 3:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500

Publications

• 30622327

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