Alport Syndrome Precision Panel
Alport Syndrome (AS) is a progressive hereditary renal disease characterized by sensorineural hearing loss, ocular abnormalities and increased risk of chronic kidney failure.
Overview
- Alport Syndrome (AS) is a progressive hereditary renal disease characterized by sensorineural hearing loss, ocular abnormalities and increased risk of chronic kidney failure. It is a genetically and phenotypically heterogeneous disorder of glomerular, cochlear and ocular basement membranes due to a mutation in the genes encoding type IV collagen. Individuals affected by this disease experience progressive loss of kidney function, presenting as blood in the urine (hematuria). The mode of inheritance can be X-linked, autosomal recessive and autosomal dominant.
- The Igenomix Alport Syndrome Precision Panel can be used to make a directed and accurate diagnosis 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 Alport Syndrome Precision Panel is indicated for those patients with a clinical suspicion or diagnosis of Alport Syndrome presenting with:
- Blood in urine (hematuria)
- Protein in urine (proteinuria)
- Edema
- Hypertension
- Hearing loss
- Ocular manifestations: anterior lenticonus, dot-and-fleck retinopathy, posterior polymorphous corneal dystrophy, temporal macular thinning etc
- Leiomyomatosis
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 symptomatic care, medical care, continuous monitoring of kidney function, and if necessary, renal transplantation.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
Genes & Diseases
See all genes and diseases
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ACSL4 | Alport Syndrome-Intellectual Disability- Midface Hypoplasia-Elliptocytosis Syndrome, X-linked Non- Syndromic Intellectual Disability |
X,XD,G |
99.97 |
NA of NA |
| AMMECR1 | Alport Syndrome-Intellectual Disability- Midface Hypoplasia-Elliptocytosis Syndrome |
X,XR,G |
99.81 |
NA of NA |
| COL4A3 | Autosomal Dominant Alport Syndrome, Autosomal Recessive Alport Syndrome, Benign Familial Hematuria |
AD,AR |
100 |
277 of 280 |
| COL4A4 | Autosomal Recessive Alport Syndrom, Benign Familial Hematuria |
AD,AR |
99.95 |
247 of 251 |
| COL4A5 | X-linked Alport Syndrome |
X,XD,G |
99.88 |
NA of NA |
| KCNE5 | Alport Syndrome-Intellectual Disability- Midface Hypoplasia-Elliptocytosis Syndrome |
99.66 |
NA of NA |
*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
Nozu, K., Nakanishi, K., Abe, Y., Udagawa, T., Okada, S., Okamoto, T., Kaito, H., Kanemoto, K., Kobayashi, A., Tanaka, E., Tanaka, K., Hama, T., Fujimaru, R., Miwa, S., Yamamura, T., Yamamura, N., Horinouchi, T., Minamikawa, S., Nagata, M., & Iijima, K. (2019). A review of clinical characteristics and genetic backgrounds in Alport syndrome. Clinical and experimental nephrology, 23(2), 158–168. https://doi.org/10.1007/s10157-018-1629-4
Kashtan C. E. (2021). Alport Syndrome: Achieving Early Diagnosis and Treatment. American journal of kidney diseases : the official journal of the National Kidney Foundation, 77(2), 272–279. https://doi.org/10.1053/j.ajkd.2020.03.026
Savige, J., Gregory, M., Gross, O., Kashtan, C., Ding, J., & Flinter, F. (2013). Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. Journal of the American Society of Nephrology : JASN, 24(3), 364–375. https://doi.org/10.1681/ASN.2012020148
Zhang, Y., & Ding, J. (2017). Renal, auricular, and ocular outcomes of Alport syndrome and their current management. Pediatric Nephrology, 33(8), 1309-1316. doi: 10.1007/s00467-017-3784-3
Gross, O. (2008). Understanding renal disorders as systemic diseases: the fascinating world of basement membranes beyond the glomerulus. Nephrology Dialysis Transplantation, 23(6), 1823-1825. doi: 10.1093/ndt/gfn129
Savige, J., Ariani, F., Mari, F., Bruttini, M., Renieri, A., Gross, O., Deltas, C., Flinter, F., Ding, J., Gale, D. P., Nagel, M., Yau, M., Shagam, L., Torra, R., Ars, E., Hoefele, J., Garosi, G., & Storey, H. (2019). Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Pediatric nephrology (Berlin, Germany), 34(7), 1175–1189. https://doi.org/10.1007/s00467-018-3985-4
