Nephrotic Syndrome Precision Panel
Nephrotic Syndrome (NS) is defined as the presence of nephrotic-range proteinuria with a low serum albumin level, edema and hypercholesterolemia, indicating damage to the glomerular filtration barrier.
Overview
- Nephrotic Syndrome (NS) is defined as the presence of nephrotic-range proteinuria with a low serum albumin level, edema and hypercholesterolemia, indicating damage to the glomerular filtration barrier. Nephrotic-range proteinuria is known as the loss of 3.5 grams or more per day of protein in the urine. Nephrotic syndrome has a plethora of causes in which we can find primary kidney diseases such as minimal change disease, focal segmental glomerulosclerosis and membranous glomerulonephritis, among others. It can also be the result of systemic diseases that involve other organs apart from the kidney such as diabetes, lupus erythematosus and amyloidosis. Genetic causes of nephrotic syndrome consist of defects in glomerular filtration involving a variety of gene mutations, inherited in its majority in an autosomal recessive pattern.
- The Igenomix Nephrotic Syndrome Precision Panel can be used to make a directed and accurate differential diagnosis of proteinuria ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
- The Igenomix Nephrotic Syndrome Precision Panel is indicated for those patients with a clinical suspicion or diagnosis of Nephrotic Syndrome presenting with:
- Massive proteinuria (>3.5g/24 hours)
- Edema
- Thrombosis and embolic events
- Hypertension
- Increased susceptibility to infection
- Low albumin level
- Hyperlipidemia
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team in the form of medical care with steroids, lipid lowering drugs, preventive anticoagulation or management of underlying systemic disease.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
- Translation of genomic-informed medicine allowing for the improvement of the understanding of molecular anatomy of nephrotic syndrome and thus, the ability to care for patients.
Genes & Diseases
See all genes and diseases
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ADA | Severe Combined Immunodeficiency, Omenn Syndrome |
AR |
100 |
97 of 98 |
| ANLN | Focal Segmental Glomerulosclerosis |
AD |
99.45 |
6 of 6 |
| APOA1 | Familial Visceral Amyloidosis, Apolipoprotein A-1 Deficiency |
AD |
99.89 |
68 of 70 |
| ARHGDIA | Nephrotic Syndrome |
AR |
99.41 |
3 of 3 |
| ARL6 | Bardet-Biedl Syndrome, Retinitis Pigmentosa |
AD,AR,X,XR,G |
100 |
17 of 21 |
| AVIL | Nephrotic Syndrome |
AR |
100 |
4 of 4 |
| B2M | Familial Visceral Amyloidosis, Hypercatabolic Hypoproteinemia, Variant Abeta2m Amyloidosis |
AD,AR |
100 |
4 of 4 |
| BBIP1 | Bardet-Biedl Syndrome |
AR |
99.88 |
1 of 1 |
| BBS1 | Bardet-Biedl Syndrome |
AR |
100 |
102 of 105 |
| BBS10 | Bardet-Biedl Syndrome |
AR |
100 |
114 of 114 |
| BBS12 | Bardet-Biedl Syndrome |
AR |
99.78 |
61 of 61 |
| BBS2 | Bardet-Biedl Syndrome, Retinitis Pigmentosa |
AR |
100 |
99 of 100 |
| BBS4 | Bardet-Biedl Syndrome |
AR |
100 |
45 of 48 |
| BBS5 | Bardet-Biedl Syndrome |
AR |
99.8 |
30 of 31 |
| BBS7 | Bardet-Biedl Syndrome |
AR |
100 |
48 of 48 |
| BBS9 | Bardet-Biedl Syndrome |
AR |
99.56 |
50 of 51 |
| C1QBP | Combined Oxidative Phosphorylation Deficiency |
AR |
99.89 |
6 of 6 |
| C3 | Autosomal Recessive Complement Component 3 Deficiency, Atypical Hemolytic Uremic Syndrome |
AD,AR |
100 |
123 of 124 |
| C8ORF37 | Bardet-Biedl Syndrome, Cone-Rod Dystrophy, Retinitis Pigmentosa |
AD,AR,X,XR,G |
na |
na |
| CASP10 | Autoimmune Lymphoproliferative Syndrome, Type IIa |
AD |
99.86 |
6 of 6 |
| CCND1 | Multiple Myeloma, Von Hippel-Lindau Syndrome |
AD |
99.95 |
1 of 1 |
| CEP290 | Bardet-Biedl Syndrome, Joubert Syndrome, Leber Congenital Amaurosis, Meckel Syndrome, Senior- Loken Syndrome |
AR |
96.47 |
293 of 327 |
| CHD7 | Charge Syndrome, Omenn Syndrome |
AD |
96.25 |
823 of 896 |
| CHST14 | Musculocontractural Ehlers-Danlos Syndrome |
AR |
97.7 |
21 of 22 |
| COL4A3 | Autosomal Dominant Alport Syndrome, Autosomal Recessive Alport Syndrome, Benign Familial Hematuria |
AD,AR |
100 |
277 of 280 |
| COL4A4 | Autosomal Recessive Alport Syndrome, Benign Familial Hematuria |
AD,AR |
99.95 |
247 of 251 |
| COL4A5 | X-linked Alport Syndrome |
X,XD,G |
99.88 |
NA of NA |
| COQ2 | Coenzyme Q10 Deficiency, Multiple System Atrophy, Leigh Syndrome With Nephrotic Syndrome |
AD,AR |
99.61 |
37 of 38 |
| COQ6 | Coenzyme Q10 Deficiency |
AR |
100 |
19 of 19 |
| COQ8B | Nephrotic Syndrome |
AR |
100 |
NA of NA |
| CRB2 | Ventriculomegaly With Cystic Kidney Disease, Focal Segmental Glomerulosclerosis |
AR |
99.5 |
26 of 29 |
| CYBC1 | Autosomal Recessive Chronic Granulomatous Disease |
AR |
na |
na |
| DCLRE1C | Omenn Syndrome, Severe Combined Immunodeficiency With Sensitivity To Ionizing Radiation, Omenn Syndrome |
AR |
99.99 |
72 of 73 |
| DGKE | Nephrotic Syndrome |
AR |
99.67 |
41 of 42 |
| DHX37 | 46,XY Sex Reversal, 46,XY Partial Gonadal Dysgenesis, Neurodevelopmental Disorder With Brain Anomalies And With Or Without Vertebral Or Cardiac Anomalies, Testicular Regression Syndrome |
AD,AR |
99.87 |
13 of 13 |
| DMRT3 | 46,XY Partial Gonadal Dysgenesis |
– |
88.67 |
1 of 1 |
| EMP2 | Familial Idiopathic Steroid-Resistant Nephrotic Syndrome |
AR |
99.98 |
3 of 3 |
| FGA | Afibrinogenemia, Congenital Hypofibrinogenemia, Familial Visceral Amyloidosis, Familial Dysfibrinogenemia |
AD,AR |
100 |
153 of 154 |
| FN1 | Glomerulopathy With Fibronectin Deposits, Fibronectin Glomerulopathy |
AD |
100 |
34 of 34 |
| FOXP3 | Immunodysregulation, X-linked Polyendocrinopathy And Enteropathy |
X,XR,G |
99.86 |
NA of NA |
| GATA3 | Hypoparathyroidism, Sensorineural Deafness, And Renal Disease |
AD |
100 |
81 of 81 |
| GATA4 | Testicular Anomalies With Or Without Congenital Heart Disease, 46,XY Partial Gonadal Dysgenesis, 8p23.1 Microdeletion Syndrome |
AD |
94.69 |
108 of 130 |
| GLA | Fabry Disease |
X,XR,G |
98 |
NA of NA |
| GSN | Amyloidosis |
AD |
96.69 |
16 of 17 |
| IFIH1 | Aicardi-Goutieres Syndrome, Singleton-Merten Syndrome |
AD |
99.62 |
26 of 27 |
| IFT172 | Retinitis Pigmentosa, Bardet-Biedl Syndrome, Jeune Syndrome, Retinitis Pigmentosa |
AR |
100 |
37 of 37 |
| IFT27 | Bardet-Biedl Syndrome |
AR |
100 |
5 of 5 |
| IL2RG | X-linked Severe Combined Immunodeficiency, Omenn Syndrome |
X,XR,G |
99.86 |
NA of NA |
| IL7R | Autosomal Recessive Severe Combined Immunodeficiency, Omenn Syndrome |
AR |
100 |
54 of 55 |
| IRAK1 | Pediatric Systemic Lupus Erythematosus |
– |
96.2 |
NA of NA |
| ITGA3 | Interstitial Lung Disease, Nephrotic Syndrome, And Congenital Epidermolysis Bullosa |
AR |
99.2 |
11 of 11 |
| JAK1 | Autoinflammation, Immune Dysregulation, And Eosinophilia |
AD |
99.92 |
7 of 8 |
| KANK2 | Nephrotic Syndrome, Palmoplantar Keratoderma And Woolly Hair |
AR |
99.92 |
3 of 3 |
| LAGE3 | X-linked Galloway -Mowat Syndrome |
X,XR,G |
91.36 |
NA of NA |
| LAMB2 | Nephrotic Syndrome With Or Without Ocular Abnormalities, Pierson Syndrome, Synaptic Congenital Myasthenic Syndromes |
AR |
100 |
129 of 129 |
| LIG4 | LIG4 Syndrome, Multiple Myeloma, Dubowitz Syndrome, Omenn Syndrome |
AR |
99.48 |
46 of 46 |
| LMNB2 | Barraquer-Simons Syndrome, Progressive Myoclonic Epilepsy, Acquired Partial Lipodystrophy |
AD,AR |
95.03 |
5 of 5 |
| LMX1B | Nail-Patella Syndrome, 9q33.3q34.11 Microdeletion Syndrome, Nail-Patella-Like Renal Disease |
AD |
100 |
191 of 191 |
| LYZ | Familial Visceral Amyloidosis |
AD |
100 |
10 of 10 |
| LZTFL1 | Bardet-Biedl Syndrome |
AR |
99.83 |
4 of 4 |
| MAGI2 | Nephrotic Syndrome |
AR |
93.82 |
7 of 9 |
| MAP3K1 | 46,XY Sex Reversal, 46,XY Complete Gonadal Dysgenesis, 46,XY Partial Gonadal Dysgenesis |
AD |
96.5 |
31 of 32 |
| MARS1 | Charcot-Marie- Tooth Disease, Interstitial Lung And Liver Disease |
AD,AR |
99.98 |
19 of 19 |
| MEFV | Familial Mediterranean Fever, Behçet Disease |
AD,AR |
96.77 |
174 of 188 |
| MKKS | Bardet-Biedl Syndrome, Mckusick-Kaufman Syndrome |
AR |
89.96 |
71 of 71 |
| MKS1 | Bardet-Biedl Syndrome, Joubert Syndrome, Meckel Syndrome |
AR |
99.98 |
49 of 49 |
| MME | Charcot-Marie-Tooth Disease, Spinocerebellar Ataxia, Congenital Membranous Nephropathy Due To Fetomaternal Anti-Neutral Endopeptidase Alloimmunization |
AD,AR |
100 |
33 of 33 |
| MYO1E | Focal Segmental Glomerulosclerosis |
AR |
100 |
30 of 30 |
| NLRP3 | Cinca Syndrome, Familial Cold Inflammatory Syndrome, Keratoendotheliitis Fugax Hereditaria, Muckle-Wells Syndrome |
AD |
100 |
152 of 152 |
| NPHP1 | Nephronophthisis, Senior-Loken Syndrome, Bardet-Biedl Syndrome, Joubert Syndrome With Renal Defect |
AR |
100 |
58 of 59 |
| NPHS1 | Congenital Nephrotic Syndrome |
AR |
100 |
351 of 352 |
| NPHS2 | Autosomal Recessive Steroid-Resistant Nephrotic Syndrome |
AR |
99.7 |
209 of 212 |
| NR0B1 | Congenital Adrenal Hypoplasia, 46,XX Testicular Disorder Of Sex Development, 46,XY Complete Gonadal Dysgenesis , 46,XY Partial Gonadal Dysgenesis |
X,XR,G |
99.87 |
NA of NA |
| NR5A1 | 46,XX Sex Reversal, 46,XY Sex Reversal, 46,XX Gonadal Dysgenesis, 46,XX Ovotesticular Disorder Of Sex Development, 46,XX Testicular Disorder Of Sex Development |
AD |
99.97 |
222 of 224 |
| NUP107 | Galloway-Mowat Syndrome, Nephrotic Syndrome, Ovarian Dysgenesis, 46,XX Gonadal Dysgenesis |
AR |
99.91 |
15 of 15 |
| NUP133 | Galloway-Mowat Syndrome, Nephrotic Syndrome |
AR |
99.94 |
6 of 6 |
| NUP160 | Nephrotic Syndrome |
AR |
99.96 |
3 of 3 |
| NUP205 | Nephrotic Syndrome |
AR |
98.95 |
6 of 6 |
| NUP85 | Nephrotic Syndrome |
AR |
97.59 |
5 of 5 |
| NUP93 | Nephrotic Syndrome |
AR |
99.91 |
16 of 17 |
| OSGEP | Galloway-Mowat Syndrome |
AR |
99.17 |
19 of 19 |
| PAX2 | Focal Segmental Glomerulosclerosis, Papillorenal Syndrome, Renal Coloboma Syndrome |
AD |
99.99 |
100 of 100 |
| PDSS2 | Primary Coenzyme Q10 Deficiency, Leigh Syndrome With Nephrotic Syndrome |
AR |
99.99 |
6 of 6 |
| PLCE1 | Nephrotic Syndrome |
AR |
99.93 |
73 of 73 |
| PMM2 | Congenital Disorder Of Glycosylation Type Ia |
AR |
100 |
127 of 129 |
| PRKCD | Common Variable Immunodeficiency, Autoimmune Lymphoproliferative Syndrome |
AR |
100 |
9 of 9 |
| PTPRO | Nephrotic Syndrome |
AR |
99.99 |
10 of 10 |
| PUS3 | Autosomal Recessive Mental Retardation, Severe Growth Deficiency-Strabismus -Extensive Dermal Melanocytosis-Intellectual Disability Syndrome |
AR |
99.01 |
8 of 9 |
| RAG1 | Combined Cellular And Humoral Immune Defects With Granulomas, Omenn Syndrome, Autosomal Recessive Severe Combined Immunodeficiency |
AR |
100 |
193 of 193 |
| RAG2 | Combined Cellular And Humoral Immune Defects With Granulomas, Omenn Syndrome, Autosomal Recessive Severe Combined Immunodeficiency |
AR |
100 |
90 of 91 |
| RMRP | Anauxetic Dysplasia, Cartilage-Hair Hypoplasia, Metaphyseal Dysplasia Without Hypotrichosis, Omenn Syndrome |
AR |
na |
na |
| SAA1 | Amyloidosis | – |
98.45 |
0 of 1 |
| SCARB2 | Action Myoclonus-Renal Failure Syndrome, Gaucher Disease Type 1, Unverricht-Lundborg Disease |
AR |
99.95 |
29 of 29 |
| SDCCAG8 | Bardet-Biedl Syndrome, Senior-Loken Syndrome |
AR |
96.29 |
18 of 19 |
| SERPINA1 | Alpha-1-Antitrypsin Deficiency |
AR |
99.77 |
107 of 111 |
| SGPL1 | Nephrotic Syndrome |
AR |
98.96 |
18 of 18 |
| SLC17A5 | Infantile Sialic Acid Storage Disorder |
AR |
99.91 |
49 of 49 |
| SLC35A2 | X-linked Congenital Disorder Of Glycosylation |
X,XD,G |
99.97 |
NA of NA |
| SMARCAL1 | Schimke Immuno- Osseous Dysplasia |
AR |
99.94 |
93 of 93 |
| SNAP29 | Cerebral Dysgenesis, Neuropathy, Ichthyosis, And Palmoplantar Keratodermasyndrome, Cednik Syndrome |
AR |
100 |
13 of 13 |
| SOX9 | Campomelic Dysplasia, 46,XX Ovotesticular Disorder Of Sex Development , 46,XX Testicular Disorder Of Sex Development , 46,XY Complete Gonadal Dysgenesis, 46,XY Partial Gonadal Dysgenesis, Isolated Pierre Robin Syndrome |
AD |
97.28 |
87 of 95 |
| SPP1 | Pediatric Systemic Lupus Erythematosus |
– |
99.77 |
2 of 2 |
| SRY | 46,XX Sex Reversal, 46,XY Sex Reversal, 45,X/46,XY Mixed Gonadal Dysgenesis, 46,XX Ovotesticular Disorder Of Sex Development , 46,XX Testicular Disorder Of Sex Development, 46,XY Complete Gonadal Dysgenesis, 46,XY Partial Gonadal Dysgenesis |
X,XD,Y,G |
45 |
NA of NA |
| STAT4 | Behçet Disease, Pediatric Systemic Lupus Erythematosus |
99.98 |
4 of 4 | |
| TBC1D8B | Nephrotic Syndrome |
X,G |
98.21 |
NA of NA |
| TBX18 | Congenital Anomalies Of Kidney And Urinary Tract |
AD |
99.8 |
9 of 12 |
| TP53RK | Galloway-Mowat Syndrome |
AR |
97.68 |
5 of 5 |
| TPRKB | Galloway-Mowat Syndrome |
AR |
85.66 |
2 of 2 |
| TRIM32 | Bardet-Biedl Syndrome |
AR |
100 |
17 of 17 |
| TRPC6 | Focal Segmental Glomerulosclerosis |
AD |
99.92 |
52 of 55 |
| TTC8 | Bardet-Biedl Syndrome, Retinitis Pigmentosa |
AR |
99.33 |
28 of 28 |
| VAMP7 | 46,XY Partial Gonadal Dysgenesis |
99.98 |
NA of NA | |
| VPS33A | Mucopolysaccharidosis -Plus Syndrome |
AR |
97.86 |
1 of 1 |
| WDPCP | Bardet-Biedl Syndrome, Heart Defect-Tongue Hamartoma-Polysyndactyly Syndrome, Meckel Syndrome |
AR |
99.3 |
8 of 8 |
| WDR4 | Galloway-Mowat Syndrome, Microcephaly, Growth Deficiency, Seizures, And Brain Malformations |
AR |
99.91 |
7 of 7 |
| WDR73 | Galloway-Mowat Syndrome, Camos Syndrome |
AR |
95.71 |
14 of 14 |
| WT1 | Denys-Drash Syndrome, Frasier Syndrome, Nephrotic Syndrome, Wilms Tumor, Aniridia, Genitourinary Anomalies, And Mental Retardation Syndrome Chromosome 11p13 Deletion Syndrome 46,XY Complete Gonadal Dysgenesis, 46,XY Partial Gonadal Dysgenesis, Meacham Syndrome |
AD |
98.92 |
178 of 185 |
| WWOX | 46,XY Partial Gonadal Dysgenesis, Autosomal Recessive Cerebellar Ataxia-Epilepsy -Intellectual Disability Syndrome Due To Wwox Deficiency |
AR |
99.94 |
44 of 44 |
| ZAP70 | Multisystem Autoimmune Disease, Atypical Severe Combined Immunodeficiency |
AR |
99.99 |
30 of 30 |
| ZFPM2 | 46,XY Sex Reversal, 46,XY Partial Gonadal Dysgenesis |
AD |
99.4 |
44 of 46 |
| ZNF592 | Camos Syndrome | – |
99.93 |
1 of 1 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
Shin, J. I., Kronbichler, A., Oh, J., & Meijers, B. (2018). Nephrotic Syndrome: Genetics, Mechanism, and Therapies. BioMed research international, 2018, 6215946. https://doi.org/10.1155/2018/6215946
Rood, I., Deegens, J., Lugtenberg, D., Bongers, E., & Wetzels, J. (2019). Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling. American Journal Of Kidney Diseases, 73(3), 400-403. doi: 10.1053/j.ajkd.2018.06.034
Sharief, S. N., Hefni, N. A., Alzahrani, W. A., Nazer, I. I., Bayazeed, M. A., Alhasan, K. A., Safdar, O. Y., El-Desoky, S. M., & Kari, J. A. (2019). Genetics of congenital and infantile nephrotic syndrome. World journal of pediatrics : WJP, 15(2), 198–203. https://doi.org/10.1007/s12519-018-00224-0
Watanabe, A., Feltran, L. S., & Sampson, M. G. (2019). Genetics of Nephrotic Syndrome Presenting in Childhood: Core Curriculum 2019. American journal of kidney diseases : the official journal of the National Kidney Foundation, 74(4), 549–557. https://doi.org/10.1053/j.ajkd.2019.01.033
Eddy, A. A., & Symons, J. M. (2003). Nephrotic syndrome in childhood. Lancet (London, England), 362(9384), 629–639. https://doi.org/10.1016/S0140-6736(03)14184-0
Braun, D. A., Rao, J., Mollet, G., Schapiro, D., Daugeron, M. C., Tan, W., Gribouval, O., Boyer, O., Revy, P., Jobst-Schwan, T., Schmidt, J. M., Lawson, J. A., Schanze, D., Ashraf, S., Ullmann, J., Hoogstraten, C. A., Boddaert, N., Collinet, B., Martin, G., Liger, D., … Hildebrandt, F. (2017). Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nature genetics, 49(10), 1529–1538. https://doi.org/10.1038/ng.3933
