Proteinuric renal disease

Gene: NOS1AP

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 1:52 p.m. | Last Modified: 4 Dec 2024, 1:52 p.m.

Panel Version: 4.22

Comment on list classification: As reviewed by Zornitza Stark and reported in PMID:33523862, there are two unrelated individuals with homozygous NOS1AP variants (c.428G>A/ p.Cys143Tyr & c.345-3T-G) and presenting with nephrotic syndrome, type 22 (MIM# 619155).

Introduction of patient variant (c.428G>A) has resulted in aberrant glomeruli formation in kidney organoids. In addition, homozygous exon 3-deleted mice recapitulated the human phenotype, exhibiting proteinuria, foot process effacement, and glomerulosclerosis.

Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.

Created: 24 Jan 2024, 7:58 p.m. | Last Modified: 24 Jan 2024, 7:58 p.m.

Panel Version: 4.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 22, OMIM:619155

Publications

• 33523862

Green List (high evidence)

Nephrotic syndrome type 22 (NPHS22) is an autosomal recessive renal disease characterized by onset of progressive kidney dysfunction in infancy. Affected individuals usually present with edema associated with hypoproteinemia, proteinuria, and microscopic hematuria. Renal biopsy shows effacement of the podocyte foot processes, glomerulosclerosis, and thickening of the glomerular basement membrane. The disease is steroid-resistant and progressive, resulting in end-stage renal disease usually necessitating kidney transplant. Two unrelated families and animal model.

No PMID yet: https://advances.sciencemag.org/content/7/1/eabe1386
Sources: Literature

Created: 1 Feb 2021, 9:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 22, MIM# 619155

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