Proteinuric renal disease

Gene: CD151

Green List (high evidence)

Positive case in UK renal panel test. Confirmed homozygous likely pathogenic nonsense variant. Supporting biopsy showed CD151 expression was significantly reduced by immunostaining. Functional studies undertaken showing CRISPR-Cas9 depletion of cd151 in zebrafish caused proteinuria.

Created: 17 Jun 2021, 11:33 a.m. | Last Modified: 17 Jun 2021, 11:33 a.m.

Panel Version: 2.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephropathy with pretibial epidermolysis bullosa and deafness #609057

Publications

• PMID: 15265795
• 29138120
• 17015618
• 32641585
• 22338088
• 18787104
• 22201679

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

Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.

Created: 16 Oct 2020, 8:05 a.m. | Last Modified: 16 Oct 2020, 8:05 a.m.

Panel Version: 2.29

Green List (high evidence)

Three families described in the literature.

Created: 30 Jan 2020, 3:18 a.m. | Last Modified: 30 Jan 2020, 3:18 a.m.

Panel Version: 2.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057

Publications

• 15265795
• 29138120

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

Red List (low evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 7 Mar 2022, 11:37 p.m. | Last Modified: 7 Mar 2022, 11:37 p.m.

Panel Version: 2.66

Comment on list classification: Further case reported by Natalie Forrester from the South West Genomic Laboratory Hub, which supports the recommendation for a green rating.

Created: 18 Aug 2021, 4:08 p.m. | Last Modified: 18 Aug 2021, 4:08 p.m.

Panel Version: 2.55

Comment on list classification: 3 cases reported plus mouse model

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

Panel Version: 2.20

Associated with Nephropathy with pretibial epidermolysis bullosa and deafness #609057 in OMIM (no inheritance pattern given). 2 patients are described as having proteinuria in the nephrotic range among other features.

3 cases (but 2 have the same variant - founder effect?) plus mouse model that replicates the kidney phenotype:

PMID: 15265795 - Karamatic Crew et al 2004 - report two sibs and a third unrelated patient, all of Indian Jewish origin who lack the MER2 antigen and have made anti-MER2. All had end-stage kidney disease. The two sibs had other phenotypic features such as pretibial bullous skin lesions, neurosensory deafness, bilateral lacrimal duct stenosis, nail dystrophy, and β-thalassemia minor. Less information available about the 3rd patient. Direct sequencing of all CD151 exons revealed a homozygous single nucleotide insertion G383 which causes a frameshift after Lys127, introducing a premature stop signal at codon 140. Ages of patients are not given.

PMID: 29138120 - Vahidnezhad et al 2018 - report 1 consangineous family with Epidermolysis bullosa which was screened using a gene panel and NGS. A homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) was found. In this family the 33-year old proband, initially diagnosed as Kindler syndrome, had widespread blistering, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. (Abstract only accessed).

PMID: 17015618 - Sachs et al 2006 - report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. The skin and hearing phenotypes were not observed.

Created: 31 Mar 2020, 12:59 p.m. | Last Modified: 31 Mar 2020, 1:36 p.m.

Panel Version: 2.23

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: CD151; Suggested initial gene rating: red; Evidence for inclusion: PMID: 15265795; Other comments: One family in the literature, part of syndromic presentation similar to Alports. Some in vitro evidence supporting CD151 in this phenotype (PMID: 17015618)

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
Unknown

Phenotypes
Nephropathy with pretibial epidermolysis bullosa and deafness #609057

Publications

• PMID: 15265795

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

Comment on list classification: Only 1 family, syndromic condition.

Created: 16 May 2016, 8:17 p.m.

I don't know

Currently on UK diagnostic panel, but no positive cases over 300 tested. Listed in one review. Presumed recessive

Created: 19 Oct 2015, 2:01 p.m.

Mode of inheritance
Other

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