Alport Syndrome

Alport syndrome (AS) is a progressive glomerulonephritis associated with sensorineural hearing loss with a prevalence of about 1 in 50,000 live births. X-linked Alport syndrome usually manifests in affected males with microscopic hematuria and progressive sensorineural hearing loss during childhood or adolescence. Later, patients develop proteinuria andprogressive renal failure, which eventually leads to end-stage renal disease in their 30s and 40s. Ocular symptoms are also common and may include maculopathy, posterior polymorphous dystrophy, and recurrent corneal erosion. Anterior lenticonus is considered to be virtually pathognomonic for Alport syndrome. X-linked Alport syndrome is semi-dominant and often manifests in female carriers. Approximately 90% of female carriers have microscopic hematuria, which can lead to renal failure later in life. Hearing loss is less frequent in female carriers, with a later age of onset. Alport syndrome with diffuse leiomyomatosis is a contiguous gene deletion syndrome. The submicroscopic genomic deletions involve the COL4A5 gene and parts of the adjacent COL4A6 gene. This disorder is characterized by features of Alport syndrome and by leiomyomatosis of the esophagus and tracheobronchial tree. It manifests in late childhood and can include dysphagia, postprandial vomiting, epigastric pain, recurrent bronchitis, dyspnea, cough, and stridor. Affected females may also have genital leiomyomas. Alport syndrome associated with mental retardation, midface hypoplasia and elliptocytosis is another contiguous gene deletion syndrome involving COL4A5 and FACL4, which encodes a long-chain acyl-CoA synthetase

Tests Available

Forms and Documents

Test Details

COL4A5
  • Confirmation of a clinical diagnosis
  • Differentiation between X-linked and autosomal recessive or dominant forms of the disease
  • Carrier detection in female relatives of an affected male
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

281
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Brushes

Billing

81408x1
No
Yes
  • 585.9 Chronic kidney disease, unspecified Chronic renal disease Chronic renal failure NOS, Chronic renal insufficiency
  • 743.8 Other specified anomalies of eye
  • 389.1 Sensorineural hearing loss, Perceptive hearing loss or deafness
  • 583.9 With unspecified pathological lesion in kidney Glomerulitis NOS, Glomerulonephritis NOS, Nephritis NOS, Nephropathy NOS
* For price inquiries please email zebras@genedx.com

References

  1. Arrondel C et al (2004) Kidney Int 65:2030-2040
  2. Gross O et al (2002). Nephrol Dial Transplant 17:1218-1227
  3. Hertz JM et al (2001). Human Mutation 18:141-148
  4. Kashtan C (1999). Medicine (Baltimore) 78:338-360
  5. Kashtan C (Updated 01-08-2007) Collagen IV-Related Nephropathies (Alport Syndrome and Thin Basement Membrane Nephropathy)
  6. Martin, P et al (1998). J Am Soc Nephrol 9:2291-2301
  7. Plant K et al (1999). Human Mutation 13:124-132
  8. Vetrie et al (1992) Genomics 14(3):624-633

Forms and Documents

Test Details

ABHD12, ACTG1, ATP6V1B1, BDP1, BSND, CABP2, CACNA1D, CATSPER2, CCDC50, CD164, CDC14A, CDH23, CEACAM16, CIB2, CLDN14, CLIC5, CLPP, CLRN1, COCH, COL11A2, COL4A3, COL4A4, COL4A6, CRYM, DCDC2, DFNA5, DFNB59, DIABLO, DIAPH1, DIAPH3, EDN3, EDNRB, ELMOD3, EPS8, ESPN, ESRRB, EYA1, EYA4, FAM189A2, FAM65B, GATA3, GIPC3, GJA1, GJB1, GJB2, GJB3, GJB6, GPR98, GPSM2, GRHL2, GRXCR1, HARS, HARS2, HGF, HOMER2, HSD17B4, ILDR1, JAG1, KARS, KCNE1, KCNJ10, KCNQ1, KCNQ4, KITLG, LARS2, LHFPL5, LHX3, LOXHD1, LRTOMT, MARVELD2, MCM2, MIR96, MITF, MSRB3, MT-RNR1, MT-TL1, MT-TS1, MYH14, MYH9, MYO15A, MYO1A, MYO1C, MYO1F, MYO3A, MYO6, MYO7A, OSBPL2, OTOA, OTOF, OTOG, OTOGL, P2RX2, PAX3, PCDH15, PMP22, PNPT1, POU3F4, POU4F3, PRPS1, PTPRQ, RDX, S1PR2, SERPINB6, SIX1, SIX5, SLC17A8, SLC26A4, SLC26A5, SLITRK6, SMPX, SNAI2, SOX10, SOX2, STRC, SYNE4, TBC1D24, TECTA, TIMM8A, TJP2, TMC1, TMIE, TMPRSS3, TMPRSS5, TPRN, TRIOBP, TSPEAR, USH1C, USH1G, USH2A, WFS1, WHRN/DFNB31
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management
  • Testing of at-risk relatives for specific known variant(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies
  • Next-Gen Sequencing
  • Long Range PCR
  • MLPA
  • Multiplex junction-specific PCR
  • Sanger/ABI sequencing

Ordering

J806
6-8 weeks
2-5 mL Blood - Lavender Top Tube

Billing

81430x1, 81431x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Morton et al. (2006) N. Engl. J. Med. 354 (20):2151-64 (PMID: 16707752)
  2. Wroblewska-Seniuk et al. (2017) Pediatr. Res. : (PMID: 27861465)
  3. Hilgert et al. (2009) Mutat. Res. 681 (2-3):189-96 (PMID: 18804553)
  4. Sloan-Heggen et al. (2016) Hum. Genet. 135 (4):441-50 (PMID: 26969326)
  5. Shearer et al. (2010) Proceedings Of The National Academy Of Sciences Of The United States Of America 107 (49):21104-9 (PMID: 21078986)
  6. Sommen et al. (2016) Hum. Mutat. 37 (8):812-9 (PMID: 27068579)
  7. Venkatesh et al. (2015) Med J Armed Forces India 71 (4):363-8 (PMID: 26663965)
  8. Kochhar et al. (2007) Genet. Med. 9 (7):393-408 (PMID: 17666886)
  9. Martínez et al. (2009) Antioxid. Redox Signal. 11 (2):309-22 (PMID: 18837651)