Activity

Filter

Cancel
Date Panel Item Activity
22 actions
Proteinuric renal disease v6.18 APOE Ida Ertmanska commented on gene: APOE: Comment on mode of inheritance: There are numerous patients with proteinuria and glomerulopathy linked to APOE variants. However, most of these patients harbour monoallelic rare variants, together with a homozygous APOE2 risk allele. There seems to be only 1 case reported with biallelic rare APOE missense variants, inherited from unaffected parents (PMID: 35119017). Hence, the mode of inheritance should stay MONOALLELIC, until more evidence emerges.
Proteinuric renal disease v6.18 APOE Ida Ertmanska changed review comment from: PMID: 24570682 Kawanishi et al., 2013
Report of 3 likely Japanese cases of APOE homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 patients were homozygous for APOE p.Arg158Cys variant - NM_000041.4: c.526C>T, p.Arg176Cys - common variant, B/LB in ClinVar. Risk factor.
Case 1 - 66yo male, diagnosed with diabetes at 50 yrs, untreated; testing showed urinary abnormality of protein 3+ (urinary protein 2.07g/day) and occult blood 1+, serum creatinine level of 0.96 mg/dl; on renal biopsy, 1/11 glomeruli showed global sclerosis, and the other glomeruli showed massive foam cell infiltration in the glomerular capillaries and mildly expanded mesangium.
Case 2 - 58yo male with nephrotic syndrome; urinary protein 7.38 g/day, hypoalbuminemia (1.9 g/dl); he was treated for diabetes since the age of 50 years; renal biopsy revealed 5 of 22 glomeruli with global sclerosis; residual glomeruli showed massive foam cell infiltration in the glomerular capillaries and severely widened mesangium - foam cells stained positive for CD68.
Case 3 - 78yo male with nephrotic syndrome; medical history includes hypertension, hypothyroidism, and diabetes mellitus; urinary protein 2.5 g/day, red blood cells in urine (1–4/hpf). A kidney biopsy revealed 21 glomeruli, of which 2 were globally sclerotic. The glomeruli showed increased mesangial matrices and mild GBM thickening. Massive foam cells had infiltrated into the glomerular capillaries and mesangial region.

PMID: 29692990 Fukunaga et al., 2018
Report of a Japanese 20yo female with proteinuria (3+) and hematuria (3+); on renal biopsy, more than 30 glomeruli were contained in LM specimens, some of which showed global sclerotic change; diagnosed with membranous nephropathy. She was homozygous for APOE2 allele and heterozygous for APOE p.Ser197Cys rare variant - NM_000041.4: c.644C>G, p.Ser215Cys (not in gnomAD 4.1.1).

PMID: 31874799 Saito et al., 2020; to: PMID: 24570682 Kawanishi et al., 2013
Report of 3 likely Japanese cases of APOE homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 patients were homozygous for APOE p.Arg158Cys variant - NM_000041.4: c.526C>T, p.Arg176Cys - common variant, B/LB in ClinVar. Risk factor.
Case 1 - 66yo male, diagnosed with diabetes at 50 yrs, untreated; testing showed urinary abnormality of protein 3+ (urinary protein 2.07g/day) and occult blood 1+, serum creatinine level of 0.96 mg/dl; on renal biopsy, 1/11 glomeruli showed global sclerosis, and the other glomeruli showed massive foam cell infiltration in the glomerular capillaries and mildly expanded mesangium.

Case 2 - 58yo male with nephrotic syndrome; urinary protein 7.38 g/day, hypoalbuminemia (1.9 g/dl); he was treated for diabetes since the age of 50 years; renal biopsy revealed 5 of 22 glomeruli with global sclerosis; residual glomeruli showed massive foam cell infiltration in the glomerular capillaries and severely widened mesangium - foam cells stained positive for CD68.

Case 3 - 78yo male with nephrotic syndrome; medical history includes hypertension, hypothyroidism, and diabetes mellitus; urinary protein 2.5 g/day, red blood cells in urine (1–4/hpf). A kidney biopsy revealed 21 glomeruli, of which 2 were globally sclerotic. The glomeruli showed increased mesangial matrices and mild GBM thickening. Massive foam cells had infiltrated into the glomerular capillaries and mesangial region.

PMID: 29692990 Fukunaga et al., 2018
Report of a Japanese 20yo female with proteinuria (3+) and hematuria (3+); on renal biopsy, more than 30 glomeruli were contained in LM specimens, some of which showed global sclerotic change; diagnosed with membranous nephropathy. She was homozygous for APOE2 allele and heterozygous for APOE p.Ser197Cys rare variant - NM_000041.4: c.644C>G, p.Ser215Cys (not in gnomAD 4.1.1).

PMID: 35119017 Li et al., 2021
Report of a 28-year-old man who presented with severe proteinuria (4+), hyperlipidemia (serum total cholesterol, 7.09 mmol/L, low-density lipoprotein cholesterol [LDL-C], 6.39 mmol/L), edema of both legs, and normal serum albumin level; he was diagnosed with lipoprotein glomerulopathy. Renal biopsy revealed lipoprotein thrombi in the glomeruli. Immunofluorescence staining revealed APOE-positive deposits, particularly within the glomeruli. He was comp het for APOE variants: c.127C > T (p.Arg43Cys) & c.149G > A (p.Arg50His) - in trans, inherited from unaffected het parents. Both variants are rare in gnomAD, with no homozygotes reported.

PMID: 35950048 Koshino et al., 2022
Case report: 28-year-old Japanese man with mild proteinuria (+1) and hematuria, harbouring het APOE variant p.(Ser197Cys) and homozygous apoE2/2 risk allele. Kidney biopsy revealed mesangial proliferation, mesangial matrix expansion, and segmental spike lesion; EM showed massive deposits with various electron densities, the glomerular basement membrane (GBM) structure was partly degenerated by these deposits.
Proteinuric renal disease v6.18 APOE Ida Ertmanska changed review comment from: PMID: 24570682 Kawanishi et al., 2013
Report of 3 likely Japanese cases of APOE homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 patients were homozygous for APOE p.Arg158Cys variant - NM_000041.4: c.526C>T, p.Arg176Cys - common variant, B/LB in ClinVar. Risk factor.
Case 1 - 66yo male, diagnosed with diabetes at 50 yrs, untreated; testing showed urinary abnormality of protein 3+ (urinary protein 2.07g/day) and occult blood 1+, serum creatinine level of 0.96 mg/dl; on renal biopsy, 1/11 glomeruli showed global sclerosis, and the other glomeruli showed massive foam cell infiltration in the glomerular capillaries and mildly expanded mesangium.
Case 2 - 58yo male with nephrotic syndrome; urinary protein 7.38 g/day, hypoalbuminemia (1.9 g/dl); he was treated for diabetes since the age of 50 years; renal biopsy revealed 5 of 22 glomeruli with global sclerosis; residual glomeruli showed massive foam cell infiltration in the glomerular capillaries and severely widened mesangium - foam cells stained positive for CD68.
Case 3 - 78yo male with nephrotic syndrome; medical history includes hypertension, hypothyroidism, and diabetes mellitus; urinary protein 2.5 g/day, red blood cells in urine (1–4/hpf). A kidney biopsy revealed 21 glomeruli, of which 2 were globally sclerotic. The glomeruli showed increased mesangial matrices and mild GBM thickening. Massive foam cells had infiltrated into the glomerular capillaries and mesangial region.

PMID: 29692990 Fukunaga et al., 2018
Report of a Japanese 20yo female with proteinuria (3+) and hematuria (3+); on renal biopsy, more than 30 glomeruli were contained in LM specimens, some of which showed global sclerotic change; diagnosed with membranous nephropathy. She was heterozygous for APOE p.Ser197Cys variant - NM_000041.4: c.644C>G, p.Ser215Cys (not in gnomAD 4.1.1).

PMID: 31874799 Saito et al., 2020; to: PMID: 24570682 Kawanishi et al., 2013
Report of 3 likely Japanese cases of APOE homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 patients were homozygous for APOE p.Arg158Cys variant - NM_000041.4: c.526C>T, p.Arg176Cys - common variant, B/LB in ClinVar. Risk factor.
Case 1 - 66yo male, diagnosed with diabetes at 50 yrs, untreated; testing showed urinary abnormality of protein 3+ (urinary protein 2.07g/day) and occult blood 1+, serum creatinine level of 0.96 mg/dl; on renal biopsy, 1/11 glomeruli showed global sclerosis, and the other glomeruli showed massive foam cell infiltration in the glomerular capillaries and mildly expanded mesangium.
Case 2 - 58yo male with nephrotic syndrome; urinary protein 7.38 g/day, hypoalbuminemia (1.9 g/dl); he was treated for diabetes since the age of 50 years; renal biopsy revealed 5 of 22 glomeruli with global sclerosis; residual glomeruli showed massive foam cell infiltration in the glomerular capillaries and severely widened mesangium - foam cells stained positive for CD68.
Case 3 - 78yo male with nephrotic syndrome; medical history includes hypertension, hypothyroidism, and diabetes mellitus; urinary protein 2.5 g/day, red blood cells in urine (1–4/hpf). A kidney biopsy revealed 21 glomeruli, of which 2 were globally sclerotic. The glomeruli showed increased mesangial matrices and mild GBM thickening. Massive foam cells had infiltrated into the glomerular capillaries and mesangial region.

PMID: 29692990 Fukunaga et al., 2018
Report of a Japanese 20yo female with proteinuria (3+) and hematuria (3+); on renal biopsy, more than 30 glomeruli were contained in LM specimens, some of which showed global sclerotic change; diagnosed with membranous nephropathy. She was homozygous for APOE2 allele and heterozygous for APOE p.Ser197Cys rare variant - NM_000041.4: c.644C>G, p.Ser215Cys (not in gnomAD 4.1.1).

PMID: 31874799 Saito et al., 2020
Proteinuric renal disease v6.18 APOE Ida Ertmanska reviewed gene: APOE: Rating: GREEN; Mode of pathogenicity: None; Publications: 24570682, 29692990; Phenotypes: Lipoprotein glomerulopathy, OMIM:611771, lipoprotein glomerulopathy, MONDO:0012725; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuric renal disease v2.70 APOE Eleanor Williams Phenotypes for gene: APOE were changed from Lipoprotein glomerulopathy, MIM# 611771 to Lipoprotein glomerulopathy, OMIM:611771
Proteinuric renal disease v2.69 APOE Eleanor Williams Tag for-review was removed from gene: APOE.
Proteinuric renal disease v2.66 APOE Eleanor Williams commented on gene: APOE: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.65 APOE Eleanor Williams Source Expert Review Green was added to APOE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.28 APOE Catherine Snow Classified gene: APOE as Amber List (moderate evidence)
Proteinuric renal disease v2.28 APOE Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.28 APOE Catherine Snow Gene: apoe has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.26 APOE Eleanor Williams Tag for-review tag was added to gene: APOE.
Proteinuric renal disease v2.19 APOE Eleanor Williams commented on gene: APOE: Set Penetrance to incomplete as several reports of unaffected individuals who carry the same variants as affected individuals.
Proteinuric renal disease v2.19 APOE Eleanor Williams Source Expert list was removed from APOE.
Source Literature was added to APOE.
Penetrance for gene APOE was set from to None
Proteinuric renal disease v2.18 APOE Eleanor Williams Publications for gene: APOE were set to 10432380; 9176854; 18077821
Proteinuric renal disease v2.17 APOE Eleanor Williams Classified gene: APOE as Green List (high evidence)
Proteinuric renal disease v2.17 APOE Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to green as many published cases of variants in APOE in patients with Lipoprotein glomerulopathy
Proteinuric renal disease v2.17 APOE Eleanor Williams Gene: apoe has been classified as Green List (High Evidence).
Proteinuric renal disease v2.16 APOE Eleanor Williams changed review comment from: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

Several publications report variants in the APOE gene in association with Lipoprotein glomerulopathy, mostly in individuals of Asian ethnicity but also in those with European ancestry for example (PMID: 18077821 - Rovin et al 2007). PMID: 31092271 - Xie et al 2019 lists many of the published variants (~12 to date, mostly point mutations, but also some deletions)

In several cases clinical asymptomatic carriers (all female?) also carry the same variants as probands e.g.
PMID: 18077821 - Rovin et al 2007
PMID: 10432380 - Matsunaga et al 1999
PMID: 31092271 - Xie et al 2019




; to: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

Several publications report variants in the APOE gene in association with Lipoprotein glomerulopathy, mostly in individuals of Asian ethnicity but also in those with European ancestry (for example PMID: 18077821 - Rovin et al 2007). PMID: 31092271 - Xie et al 2019 lists many of the published variants (~12 to date, mostly point mutations, but also some deletions)

In several cases clinical asymptomatic carriers (all female?) also carry the same variants as probands e.g.
PMID: 18077821 - Rovin et al 2007
PMID: 10432380 - Matsunaga et al 1999
PMID: 31092271 - Xie et al 2019
Proteinuric renal disease v2.16 APOE Eleanor Williams changed review comment from: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

PMID: 10432380 - Matsunaga et al 1999 - 32-year-old Japanese male patient with Lipoprotein glomerulopathy, whose history included proteinuria. A heterogyzous missense variant was identified termed apo E2 (Arg25Cys) Kyoto. His asymptomatic mother was also heterogyzous for this same variant.

PMID: 9176854 - Oikawa et al 1997 - report 3 patients with LPG from two families all with the same variant apo E Arg145Pro named APOE Sendai. Only the APOE gene was looked at.

PMID: 18077821 - Rovin et al 2007 - report two unrelated American men of European ancestry who presented with edema and proteinuria in the nephrotic range. Both patients had a heterozygous C→T transition resulting in an amino acid change Arg25Cys. Several female family members were heterozygous carriers of Arg25Cys, none had clinical evidence of lipoprotein glomerulopathy.

Review to be continued; to: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

Several publications report variants in the APOE gene in association with Lipoprotein glomerulopathy, mostly in individuals of Asian ethnicity but also in those with European ancestry for example (PMID: 18077821 - Rovin et al 2007). PMID: 31092271 - Xie et al 2019 lists many of the published variants (~12 to date, mostly point mutations, but also some deletions)

In several cases clinical asymptomatic carriers (all female?) also carry the same variants as probands e.g.
PMID: 18077821 - Rovin et al 2007
PMID: 10432380 - Matsunaga et al 1999
PMID: 31092271 - Xie et al 2019
Proteinuric renal disease v2.16 APOE Eleanor Williams commented on gene: APOE
Proteinuric renal disease v2.0 APOE Zornitza Stark gene: APOE was added
gene: APOE was added to Proteinuric renal disease. Sources: Expert list
Mode of inheritance for gene: APOE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOE were set to 10432380; 9176854; 18077821
Phenotypes for gene: APOE were set to Lipoprotein glomerulopathy, MIM# 611771
Review for gene: APOE was set to GREEN
Added comment: Specific variants in Japanese/Chinese linked to the development of a glomerulopathy, characterised by proteinuria, renal failure and deposition of lipoprotein thrombi.
Sources: Expert list