Proteinuric renal disease
Gene: CRB2
Comment on list classification: > 3 unrelated cases with plausible disease causing variants in this gene.Created: 27 Mar 2019, 11:20 p.m.
Associated with Focal segmental glomerulosclerosis 9 (616220) and Ventriculomegaly with cystic kidney disease (219730) in OMIM.
PMID: 25557779 - Ebarasi et al 2015 - recessive CRB2 variants were detected in 4 unrelated families (2 from Turkey, 2 from Europe). 3 families had parental consanguinity and were homozygous for the variants. In the other family compound heterozgyous variants in CRB2 were detected. Mutations in the first 2 families were found by homozygosity mapping and/or whole-exome sequencing; mutations in the second 2 families were found by sequencing the CRB2 gene in 1,010 families with steroid-resistant nephrotic syndrome. 3 of the mutations occurred at highly conserved residues in the tenth EGF-like domain; and functional studies showed that in crb2-null zebrafish 2 of these mutations resulted in loss of protein function.
PMID: 27942854 - Udagawa et al 2017 - Whole exome sequencing was performed in a 3-year-old girl with SRNS and identified novel compound heterozygous mutations in exons 10 and 12 of CRB2 (p.Trp1086ArgfsX64 and p.Asn1184Thr). Renal pathology showed focal segmental glomerulosclerosis with effaced podocyte foot processes in a small area, with significantly decreased Crb2 expression
PMID: 29473663 - Watanabe et al 2018 - report the long-term clinicopathologic observation of a Japanese female patient with SRNS caused by a newly identified compound heterozygous mutation of CRB2 (p.Arg628Cys and p.Gly839Trp).Created: 27 Mar 2019, 11:19 p.m.
This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: CRB2; Suggested initial gene rating: green; Evidence for inclusion: PMID: 25557779; PMID: 29473663; Other comments: Multiple unrelated patients with SRNS and CRB2 variants in the literatureCreated: 4 Feb 2019, 10:41 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Focal segmental glomerulosclerosis 9 #616220; Ventriculomegaly with cystic kidney disease #219730
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: CRB2 were changed from steroid resistant nephrotic syndrome to steroid resistant nephrotic syndrome; Focal segmental glomerulosclerosis 9 #616220; Ventriculomegaly with cystic kidney disease #219730
Publications for gene: CRB2 were set to 25557779; 27942854
Gene: crb2 has been classified as Green List (High Evidence).
Source NHS GMS was added to CRB2. Rating Changed from No List (delete) to Red List (low evidence)
gene: CRB2 was added gene: CRB2 was added to Proteinuric renal disease. Sources: Literature Mode of inheritance for gene: CRB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CRB2 were set to 25557779; 27942854 Phenotypes for gene: CRB2 were set to steroid resistant nephrotic syndrome Penetrance for gene: CRB2 were set to Complete Review for gene: CRB2 was set to GREEN