Proteinuric renal disease

Gene: MAGI2

Green List (high evidence)

Comment on list classification: Rating green as there are 4 cases reported.

Created: 26 Mar 2019, 1:54 p.m.

Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that although the reported cases have slightly different phenotypes, these are sufficiently similar to have the same pathophysiological basis. Bristol also have some unpublished cases.

Created: 26 Mar 2019, 1:54 p.m.

Associated with Nephrotic syndrome, type 15 (617609) in OMIM.

PMID: 29773874 - Ashraf et al 2018 - identified homozygous truncating mutations in the MAGI2 gene (p.Gly39* and p.Tyr746*) in two individuals from unrelated families with SRNS and neurologic impairment.

PMID: 27932480 - Bierzynska et al 2017 - detected two unique frameshift mutations and one duplication in three patients (two families) presenting with congenital nephrotic syndrome. Two siblings (175 and 175S) shared the same homozygous frameshift deletion c.3998delG:p.(Gly1333Alafs*141). The patient with the sporadic case (180) exhibited compound heterozygosity: a deletion (paternal) resulting in a premature stop codon c.64_71delAGGAACCC:p.(Arg22Glyfs*7) together with a duplication (maternal) c.3526_3533dupCTGGCAGA:p.(Glu1178Aspfs*9). All three variants were absent in the ExAC database.

Created: 26 Mar 2019, 1:51 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: MAGI2; Suggested initial gene rating: green; Evidence for inclusion: PMID: 29773874; PMID: 27932480; Other comments: Two unrelated families with SRNS/SSRNS and rare hom variants in PMID: 29773874. Two unrelated families with CNS and rare hom/compound het variants in PMID: 27932480

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

Phenotypes
Nephrotic syndrome, type 15 # 617609

Publications

• PMID: 29773874
• PMID: 27932480

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