Proteinuric renal disease

Gene: AMN

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, 8:04 a.m. | Last Modified: 16 Oct 2020, 8:04 a.m.

Panel Version: 2.27

Green List (high evidence)

Proteinuria is a very well described presenting feature of this condition, it is rated Green on our Australian panel.

Created: 9 Jan 2020, 3:14 a.m. | Last Modified: 9 Jan 2020, 3:14 a.m.

Panel Version: 2.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 30691194
• 26040326

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

I don't know

The rating of this gene has been updated following NHS Genomic Medicine Service approval. The reviewers note that a homozygous splice variant in patient with Imerslund-Grasbeck syndrome has been reported.

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: Changing rating from amber to green following expert review stating that proteinuria is a well known presenting feature of IMERSLUND-GRASBECK SYNDROME. At least 3 cases with variants in AMN and proteinuria are reported in the literature.

Created: 30 Mar 2020, 3:58 p.m. | Last Modified: 30 Mar 2020, 3:58 p.m.

Panel Version: 2.16

Associated with Megaloblastic anemia-1, Norwegian type #261100 (AR) in OMIM which is also known as IMERSLUND-GRASBECK SYNDROME (IGS).

PMID: 30691194 - Pacitto et al 2019 - describe a case of IGS with urinary tract infection and mild but persistent proteinuria at onset in an 11-month-old female child. The patient was found to be compound heterzygous for a novel intronic variant c.513+5G>A thought to affect a donor splice site, and the known pathogenetic variant c.1006+34_1007-31del. Parents each had one of the variants.

PMID: 26040326 - Montgomery et al 2015 - 2 half sisters with IGS and compound heterzygous variants in AMN are reported (c.35delA, p.Gln12Argfs*5) and (c.206 T > A, p.Met69Lys). Both presented with sub-nephrotic range proteinuria.

PMID: 22631584 - Densupsoontorn et al 2012 - report a Thai boy with IGS in whom a deleterious mutation in AMN was confirmed (homozygous c.663G>A; W221X). Persistent proteinuria was reported.

Note - not all patients are described as presenting with proteinuria e.g. PMID: 14593474 (Molecular cause of IGS unknown in this case).

Created: 30 Mar 2020, 3:55 p.m. | Last Modified: 30 Mar 2020, 3:55 p.m.

Panel Version: 2.15

Comment on list classification: Changing rating from green to amber until a review of the degree of proteinuria in patients with Imerslund-Grasbeck syndrome has been done.

Created: 9 Jul 2019, 1:03 p.m. | Last Modified: 9 Jul 2019, 1:03 p.m.

Panel Version: 1.217

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: AMN; Suggested initial gene rating: amber; Evidence for inclusion: PMID: 26040326;

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Megaloblastic anemia-1, Norwegian type #261100

Publications

• PMID: 26040326

Comment on list classification: Causes proteinuria as part of Imerslund-grasbeck syndrome.

Created: 15 Apr 2016, 10:38 a.m.

Red List (low evidence)

Lack of phenotypic fit

Created: 19 Oct 2015, 1:15 p.m.