Cone-Rod Dystrophy, Autosomal Dominant

Cone-rod dystrophy (CRD) has an estimated prevalence of 1 in 40,000 individuals. CRD presents first as a macular disease or as a diffuse retinopathy with predominance of the macular involvement. The clinical signs of CRDs reflect the predominant involvement of cones, leading to decreased visual acuity in the first decade of life. However, in some cases, diffuse retinopathy affects simultaneously cones and rods, resulting in both night blindness and loss of visual acuity. The visual field testing shows central scotomas, while the periphery is spared. Fundus examination shows pigment deposits and retinal atrophy in the macular region. At a later stage, patients are legally blind, even though large parts of the peripheral visual field remain preserved. The electroretinogram (ERG), is distinguished by a more distinctive reduction of the photopic cone b-wave amplitude than the scotopic rod b-wave amplitude, compared to rod degeneration.

Tests Available

Forms and Documents

Test Details

AIPL1
  • Confirmation of a clinical diagnosis
  • To differentiate LCA from other forms of retinal dystrophy
  • recurrence risk assessment
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

379
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.53 Chorioretinal degeneration, congenital
  • 743.55 Congenital macular changes
  • 362.76 Dystrophies primarily involving the retinal pigment epithelium, Fundus flavimaculatus, Vitelliform dystrophy
  • 362.75 Other dystrophies
  • 743.56 Other retinal changes, congenital
  • 362.74 Pigmentary retinal dystrophy, Retinal dystrophy, albipunctate, Retinitis pigmentosa
* For price inquiries please email zebras@genedx.com

References

  1. )Koenekoop R (2007) Clin and Experimental Ophthalmology 35:473-485
  2. Browne SJ (2006) Invest Ophthalmol Vis Sci 47(1):34-42
  3. den Hollander AI (2006) Am J Hum Genet 79(3):556-61
  4. Ito S (2004) Invest Ophthalmol Vis Sci 45(5):1480-5
  5. Sohocki (2000) Mol. Genet. Metab. 70, 142–150
  6. Bernal S (2003) J Med Genet 40:e89
  7. den Hollander AI (2008) Progress in Retinal and Eye Research 27:391-419
  8. Hanein S (2004) Hum Mutat 23:306-317
  9. Booij J (2007) J Med Genet 42:67-75
  10. Stone E (2007) Am J Ophthalmol 144(6):791-811
  11. Koenekoop (2005) Ophthalmic Genetics 26:175-179
  12. Morimura H (1998) Proc Natl Acad Sci 95:3088–3093
  13. den Hollander (2001) Am J Hum Genet 69:198–203
  14. )den Hollander (2004) Hum Mutat 24:355-69
  15. den Hollander (1999) Nat Genet 23:217–221

Forms and Documents

Test Details

CRX
  • Confirmation of a clinical diagnosis
  • Determine if a sporadic case is recessive or dominant (de novo)
  • Carrier testing for family members of an affected individual with known mutation(s)
  • Prenatal diagnosis in at-risk pregnancies
  • Presymptomatic testing
  • Capillary Sequencing

Ordering

353
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x1
No
Yes
  • 743.53 Chorioretinal degeneration, congenital
  • 743.54 Congenital folds and cysts of posterior segment
  • 743.55 Congenital macular changes
  • 362.76 Dystrophies primarily involving the retinal pigment epithelium, Fundus flavimaculatus, Vitelliform dystrophy
  • 362.75 Other dystrophies
  • 743.56 Other retinal changes, congenital
  • 362.74 Pigmentary retinal dystrophy, Retinal dystrophy, albipunctate, Retinitis pigmentosa
* For price inquiries please email zebras@genedx.com

References

  1. Michaelides et al., (2005) Ophthalmology 112:1442-1447
  2. Kitiratschy et al., (2009) Human Mutation 30:E782-E796
  3. Downes et al., (2001) Arch Ophthalmol 119:96-105
  4. Klevering B J et al., (2004) Eur J Hum Genet.12(12):1024-32
  5. Cremers F P M et al., (1998) Hum Molec Genet 7: 355-362
  6. Allikmets, et al (1998) Gene 215: 111-122
  7. Boon CJ et al., (2008) Prog Retin Eye Res 27:213-35
  8. Sohocki et al., (2000) Mol Genet Metab 70:142–150
  9. Lotery AJ (2000) Arch Ophthalmol]. 118(4):538-43
  10. Freund CL et al., (1997) Cell. 91(4):543- 553
  11. Rivolta C et al., (2001) Hum Mutat 18: 488-498
  12. Hamel CP et al., (2007) Orphanet J Rare Dis (1)2:7
  13. Kitiratschky et al., (2008) Invest Ophthalmol Vis Sci 49:5015

Forms and Documents

Test Details

GUCA1A
  • Confirmation of a clinical diagnosis
  • To differentiate LCA from other forms of retinal dystrophy
  • Recurrence risk assessment
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

476
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.53 Chorioretinal degeneration, congenital
  • 743.55 Congenital macular changes
  • 362.76 Dystrophies primarily involving the retinal pigment epithelium, Fundus flavimaculatus, Vitelliform dystrophy
  • 362.75 Other dystrophies
  • 743.56 Other retinal changes, congenital
  • 362.74 Pigmentary retinal dystrophy, Retinal dystrophy, albipunctate, Retinitis pigmentosa
* For price inquiries please email zebras@genedx.com

References

  1. Cremers F P M et al., (1998) Hum Molec Genet 7: 355-362
  2. Klevering B J et al., (2004) Eur J Hum Genet.12(12):1024-32
  3. Sohocki et al., (2000) Mol Genet Metab 70:142–150
  4. Boon CJ et al., (2008) Prog Retin Eye Res 27:213-35
  5. Allikmets, et al (1998) Gene 215: 111-122
  6. Freund CL et al., (1997) Cell. 91(4):543- 553
  7. Lotery AJ (2000) Arch Ophthalmol]. 118(4):538-43
  8. Rivolta C et al., (2001) Hum Mutat 18: 488-498
  9. Kitiratschky et al., (2008) Invest Ophthalmol Vis Sci 49:5015
  10. Hamel CP et al., (2007) Orphanet J Rare Dis (1)2:7
  11. Downes et al., (2001) Arch Ophthalmol 119:96-105
  12. Michaelides et al., (2005) Ophthalmology 112:1442-1447
  13. Kitiratschy et al., (2009) Human Mutation 30:E782-E796
  14. Littink et al., (2010) Invest Ophthalmol Vis Sci 51(11):5943-5951
  15. Wissinger et al., (2001) Am J Hum Genet 69:722-737
  16. Wissinger et al., (2001) Am J Hum Genet 69:722-737
  17. Thiadens et al., (2010) Ophthalmology 117(4):825- 30

Forms and Documents

Test Details

RDS (PRPH2)
  • Confirmation of a clinical diagnosis
  • To differentiate adRP from other forms of retinal dystrophy
  • Recurrence risk assessment
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

299
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 362.74 Pigmentary retinal dystrophy, Retinal dystrophy, albipunctate, Retinitis pigmentosa
* For price inquiries please email zebras@genedx.com

References

  1. Browne SJ (2006) Invest Ophthalmol Vis Sci. Jan;47(1):34-42
  2. Sullivan LS (2006) Invest Ophthalmol Vis Sci. Oct;47(10):4579-88
  3. Naushin W(2007) Invest Ophthalmol Vis Sci, Mar;48(3):1330-4
  4. Dryja TP (1991) Proc. Natl. Acad. Sci. USA Vol. 88, pp. 9370-9374
  5. Riazuddin SA (2005) Invest Ophthalmol Vis Sci. Jul;46(7):2264-70
  6. Davidson et al., (2009) Am J Hum Genet 85:581-592
  7. Kajiwara K (1993) Nat Genet.Mar;3(3):208-12
  8. Gamundi MJ (2007). Mol Vis. Jun 28;13:1031-7
  9. Kennan A (2005) Trends Genet Feb;21(2):103-10
  10. Retnet http://www.sph.uth. tmc.edu/RetNet/
  11. Sullivan LS (2006) Invest Ophthalmol Vis Sci. Jul;47(7):3052-64
  12. Bunker CH (1984) Am J Ophthalmol; 97: 357–6522
  13. Ziviello C (2005). J Med Genet. Jul;42(7):e47
  14. Haim M (2002) Acta Ophthalmol Scand Suppl 80:1-34

Forms and Documents

Test Details

  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with retinal dystrophies
  • 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

Ordering

J905
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81434x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Sahel et al. (2014) Cold Spring Harb Perspect Med 5 (2):a017111 (PMID: 25324231)
  2. Kocur et al. (2002) Br J Ophthalmol 86 (7):716-22 (PMID: 12084735);
  3. Ayuso et al. (2010) Genome Med 2 (5):34 (PMID: 20519033)
  4. Finger et al. (2011) Invest. Ophthalmol. Vis. Sci. 52 (7):4381-9 (PMID: 21447690)
  5. den Hollander et al. (2006) American Journal Of Human Genetics 79 (3):556-61 (PMID: 16909394)
  6. Braun et al. (2013) Human Molecular Genetics 22 (25):5136-45 (PMID: 23918662)
  7. Zernant et al. (2014) Hum. Mol. Genet. 23 (25):6797-806 (PMID: 25082829)
  8. Bauwens et al. (2015) Hum. Mutat. 36 (1):39-42 (PMID: 25346251)
  9. Schulz et al. (2017) Invest. Ophthalmol. Vis. Sci. 58 (1):394-403 (PMID: 28118664)
  10. Beryozkin et al. (2015) Sci Rep 5 :13187 (PMID: 26306921)
  11. Lee et al. (2015) Am. J. Ophthalmol. 160 (2):354-363.e9 (PMID: 25910913)
  12. de Castro-Miro et al. (2016) PLoS ONE 11 (12):e0168966 (PMID: 28005958)
  13. Haer-Wigman et al. (2017) Eur. J. Hum. Genet. 25 (5):591-599 (PMID: 28224992)
  14. Riera et al. (2017) Sci Rep 7 :42078 (PMID: 28181551)
  15. Carss et al. (2017) Am. J. Hum. Genet. 100 (1):75-90 (PMID: 28041643)
  16. Retterer et al. (2015) Genet. Med.: (PMID: 26633542)

Forms and Documents

Test Details

ABCA4, ADAM9, AIPL1, BEST1, C8ORF37, CABP4, CACNA1F, CDH3, CDHR1, CEP290, CERKL, CNGA3, CNGB3, CRX, DRAM2, ELOVL4, GUCA1A, GUCY2D, PAX6, PITPNM3, POC1B, PROM1, RAB28, RAX2 (QRX), RDH5, RDS (PRPH2), RIMS1, RPGR, RPGRIP1, SEMA4A, TTLL5
  • Deceased visual acuity, photophobia, and loss of color vision in childhood
  • Issues with reading, focusing on an image, or blind spots in central vision (scotomas)
  • Subsequent night blindness, central vision loss, and peripheral vision loss in later stages
  • Signs of nystagmus with progression of disease
  • Next-Gen Sequencing
  • Exon Array Dx

Ordering

J956
4 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab

Billing

81404x2; 81408x1; 81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Hamel CP et al., (2007) Orphanet J Rare Dis (1)2:7
  2. Sohocki et al., (2000) Mol Genet Metab 70:142–150
  3. Allikmets, et al (1998) Gene 215: 111-122
  4. Cremers F P M et al., (1998) Hum Molec Genet 7: 355-362
  5. Klevering B J et al., (2004) Eur J Hum Genet.12(12):1024-32
  6. Littink et al., (2010) 51(11):5943-5951
  7. Thiadens et al., (2012) Opthalmology 119(4): 819-26
  8. Boulanger-Scemama et al., (2015) Orphanet J Rare Dis 10: 85
  9. Roosing S et al., (2014) Prog Retin Eye Res 42:1-26
  10. El-Haig WM et al,. (2014) Br J Opthalmol 98(12): 1718-23
  11. Aboshiha et al., (2015) Opthalmology 122:862-864
  12. Rahner et al., (2016) Opthalmic Genet 37(3): 294-300
  13. Khan and Bolz (2016) Opthalmic Genet 37(3): 301-6
  14. Sprecher et al., (2001) Nature Genet 29: 134-136
  15. Nikopoulos K (2015) Sci Rep 5:13902
  16. Shaikh RS (2015) Eur J Hum Genet 23(4): 473-80
  17. El-Asrag ME (2015) Am J Hum Genet 96(6): 948-54
  18. Sergouniotis PI et al., (2015) Invest Opthalmol Vis Sci 56(13): 8083-90
  19. Roosing S et al., (2014) Am J Hum Genet 95(2): 131-42
  20. Durlu YK et al., (2014) JAMA Opthalmol 132(10) 1185-91
  21. Beryozkin A (2014) Invest Opthalmol Vis Sci 52(2): 1149-60
  22. Riveiro-Alvarez (2015) JAMA Opthalmol 133(2):133-9
  23. Abid et al., (2006) J Med Genet 43:378-381
  24. Sergouniotis (2014) Am J Hum Genet 94(5): 760-9
  25. Bendoni et al., (2016) 25(20): 4546-4555
  26. Wang et al., (2004) Hum Mol Genet 13(10): 1025-40
  27. Yang et al., (2015) JAMA Opthalmol 133(6):653-61
  28. Khan et al. (2013) Br J Ophthalmol 97 (3):262-5
  29. Nakamura et al., (2000) Invest Ophthalmol Vis Sci 41(12):3925-32
  30. Nakamura et al. (2003) Doc Ophthalmol 107(1):3-11
  31. Boon et al. (2009) Progress In Retinal And Eye Research 28 (3):187-205
  32. Perrault et al. (2007) Human Mutation 28 (4):416
  33. Bernstein et al. (2001) Investigative Ophthalmology & Visual Science 42 (13):3331-6
  34. Dansault et al. (2007) Molecular Vision 13 :511-23