Transthyretin Amyloidosis

Transthyretin (TTR) amyloidosis is an autosomal dominant disorder caused by the deposition of insoluble amyloid fibrils around peripheral nerves and in various tissues, including the heart muscle. Based on the predominant organ involvement, several distinct subtypes have been reported. Familial amyloid polyneuropathy (FAP) aka TTR amyloid neuropathy is characterized by slowly progressive, peripheral sensorimotor polyneuropathy and autonomic dysfunction. Disease onset is usually in the third to fourth decade of life. Sensory neuropathy starts in the lower extremities with paresthesia, impaired pain and temperature sensation, followed by loss of motor function. Autonomic neuropathy usually manifests with orthostatic hypotension, constipation alternating with diarrhea, vomiting, impotence or hypohidrosis. Unrelated to neuropathy, other organs manifestations may include cardiomyopathy, vitreous opacities and CNS amyloidosis. Leptomeningeal amyloidosis aka oculoleptomeningeal amyloidosis affects predominantly the central nervous system, sometimes combined with visual impairment. Cardiac amyloidosis usually manifests in the sixth decade of life with progressive left ventricular hypertrophy and restrictive cardiomyopathy. In a subset of families with cardiac amyloidosis, peripheral neuropathy may be completely absent or very mild. Treatment: Currently, the only effective treatment for FAP is an orthotopic liver transplant to stop production of misfolded amyloid protein. In patients with severe amyloid cardiomyopathy, a heart transplant may be necessary. Different drugs designed to prevent or alleviate accumulation of TTR amyloid protein (transthyretin amyloidois inhibitors) are currently under investigation.

Tests Available

Forms and Documents

Test Details

TTR
  • Confirmation of a clinical diagnosis
  • Differentiation between cardiac amyloidosis and other cardiomypopathies
  • Carrier testing in at-risk family members
  • Prenatal diagnosis in families with a known pathogenic variant
  • Capillary Sequencing

Ordering

363
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81404x1
No
Yes
  • 277.3 Amyloidosis
  • 425.7 Nutritional and metabolic cardiomyopathy; Code first underlying disease, as: amyloidosis (277.30-277.39), beriberi (265.0), cardiac glycogenosis (271.0), mucopolysaccharidosis (277.5), thyrotoxicosis (242.0-242.9)
  • 277.39 Other amyloidosis, Hereditary cardiac amyloidosi,s Inherited systemic amyloidosis, Neuropathic (Portuguese) (Swiss) amyloidosis, Secondary amyloidosis
* For price inquiries please email zebras@genedx.com

References

  1. Seikijima Y et al. Transthyretin amyloidosis, In: GeneReviews. Last Update: March 15, 2006. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tfap
  2. Hou et al. (2007) Transthyretin and familial amyloidotic polyneuropathy FEBS 274, 1637-50
  3. Jacobson DR et al. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in Black Americans. New Eng. J. Med. 336: 466-473, 1997
  4. Coelho T et al. A study of 159 Portuguese patients with familial amyloidotic polyneuropathy (FAP) whose parents were both unaffected. J. Med. Genet. 31: 293-299, 1994
  5. Holmgren G et al. Geographical distribution of TTR met-30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate. J. Med. Genet. 31: 351-354, 1994
  6. Ikeda S et al. Asymptomatic homozygous gene carrier in a family with type I familial amyloid polyneuropathy. Europ. Neurol. 32: 308-313, 1992
  7. Holmgren G et al. Homozygosity for the transthyretin-met30-gene in seven individuals with familial amyloidosis with polyneuropathy detected by restriction enzyme analysis of amplified genomic DNA sequences. Clin. Genet. 41: 39-41, 1992
  8. Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM
  9. Ando, Y. et al. (2005) Transthyretin-related Familial Amyloidotic Polyneuropathy Arch Neurol 62, 1057-62
  10. Saraiva, M.J.M. (2001) Transthyretin Mutations in Hyperthyroxinemia and Amyloid Disease Hum Mutat 17, 493-503
  11. Sekijima et al. (2005) The biological and chemical basis for tissue-selective amyloid disease Cell 121, 73-85

Forms and Documents

Test Details

ABCC9, ACTC1, ACTN2, ALMS1, ANKRD1, BAG3, CHRM2, CRYAB, CSRP3, DES, DMD, DOLK, DSC2, DSG2, DSP, DTNA, EMD, FKTN, GATAD1, ILK, LAMA4, LAMP2, LDB3, LMNA, MIB1, MTND1, MTND5, MTND6, MTTD Mitochondrial, MTTH, MTTI, MTTK, MTTL1, MTTL2, MTTM, MTTQ, MTTS1, MTTS2, MYBPC3, MYH6, MYH7, MYPN, NEBL, NEXN, PLN, PRDM16, RAF1, RBM20, SCN5A, SGCD, TAZ, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2, VCL
  • Confirmation of a clinical diagnosis in symptomatic patients
  • Risk assessment of asymptomatic family members of a proband with DCM/LVNC
  • Differentiation of hereditary DCM from acquired (non-genetic) causes of DCM/LVNC
  • Recurrence risk calculation
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

J554
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1, 81406x1, 81407x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM Number: {115200; 604169}: {04/21/2015; 09/04/2013}: World Wide Web URL: http://omim.org/
  2. Hershberger RE, Morales A. Dilated Cardiomyopathy Overview. 2007 Jul 27 [Updated 2013 May 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://w
  3. Callis et al. (2010) Expert review of molecular diagnostics 10(3):329-351 (PMID: 20370590)
  4. Bennett et al. (2016) Cardiology Research and Practice 2016:5172308 (PMID: 26881173)
  5. Rooms et al. (2015) Acta Cardiol 70 (6):625-31 (PMID: 26717209)
  6. Hershberger RE, Kushner JD, Parks SB. Dilated Cardiomyopathy Overview. GeneReviews. 2008. www.genetests.orgHunt et al. (2005) Circulation 112(12):e154-235 (PMID: 16160202)
  7. Herman et al. (2012) The New England Journal Of Medicine 366 (7):619-628 (PMID: 22335739)

Forms and Documents

Test Details

ACTC1, ACTN2, CAV3, CSRP3, FHL1, GLA, JPH2, LAMP2, MTTG, MTTI, MTTK, MTTQ, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTR, VCL
  • Confirmation of clinical diagnosis in symptomatic patients
  • Genetic counseling and risk assessment of asymptomatic family members of a proband with HCM
  • Differentiation of hereditary HCM associated with mutations in sarcomeric genes from phenocopies, such as Fabry Disease and Amyloidosis
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

J553
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1, 81406x1, 81407x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Cirino AL, Ho C. Hypertrophic Cardiomyopathy Overview. 2008 Aug 5 [Updated 2014 Jan 16]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.n
  2. Bennett S. Pharmacogenomics. 2004;5(4):433-8 (PubMed: 15165179)Maron et al. (2003) J. Am. Coll. Cardiol. 41 (6):974-80 (PMID: 12651044)
  3. Sekijima Y, Yoshida K, Tokuda T, et al. Familial Transthyretin Amyloidosis. 2001 Nov 5 [Updated 2012 Jan 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Availab
  4. D\'souza et al. (2014) Circulation. Heart Failure 7 (5):843-9 (PMID: 25228319)
  5. Mehta A, Hughes DA. Fabry Disease. 2002 Aug 5 [Updated 2013 Oct 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.ncbi.nlm.nih.gov/book
  6. Dominic et al. (2014) Heart (British Cardiac Society) 100 (8):611-8 (PMID: 24449718)
  7. Friedrich et al. (2012) Human Molecular Genetics 21 (14):3237-54 (PMID: 22523091)
  8. B. Maron, M. Maron, & Semsarian (2012) J. Am. Coll. Cardiol. 60 (8):705-15 (PMID: 22796258)
  9. Frey, Luedde, & Katus (2012) Nature Reviews. Cardiology 9 (2):91-100 (PMID: 22027658)
  10. Ingles et al. (2015) Circ Cardiovasc Genet 8 (6):852-9 (PMID: 26671970)
  11. Hershberger et al. (2009) Journal Of Cardiac Failure 15 (2):83-97 (PMID: 19254666)
  12. Stenson et al. (2014) Human genetics 133 (1):1-9 (PMID: 24077912)
  13. Pan et al. (2012) Circulation. Cardiovascular Genetics 5 (6):602-10 (PMID: 23074333)
  14. Van Rijsingen et al. (2009) Netherlands Heart Journal : Monthly Journal Of The Netherlands Society Of Cardiology And The Netherlands Heart Foundation 17 (12):458- 63 (PMID: 20087448)
  15. Girolami et al. (2010) Journal Of The American College Of Cardiology 55 (14):1444-53 (PMID: 20359594)
  16. Gersh et al. (2011) Circulation 124 (24):2761-96 (PMID: 22068435)
  17. Olson et al. (2002) Circulation 105 (20):2337-40 (PMID: 12021217)

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Confirmation of clinical diagnosis in symptomatic patients
  • Genetic counseling and risk assessment of asymptomatic family members of a proband with HCM
  • Differentiation of hereditary HCM associated with mutations in sarcomeric genes from phenocopies, such as Fabry Disease and Amyloidosis

Customizable Cardiology Panel

  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

J553C
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1, 81406x1, 81407x2
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Cirino AL, Ho C. Hypertrophic Cardiomyopathy Overview. 2008 Aug 5 [Updated 2014 Jan 16]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.n
  2. Bennett S. Pharmacogenomics. 2004;5(4):433-8 (PubMed: 15165179)Maron et al. (2003) J. Am. Coll. Cardiol. 41 (6):974-80 (PMID: 12651044)
  3. Sekijima Y, Yoshida K, Tokuda T, et al. Familial Transthyretin Amyloidosis. 2001 Nov 5 [Updated 2012 Jan 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Availab
  4. D\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'souza et al. (2014) Circulation. Heart Failure 7 (5):843-9 (PMID: 25228319)
  5. Mehta A, Hughes DA. Fabry Disease. 2002 Aug 5 [Updated 2013 Oct 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.ncbi.nlm.nih.gov/book
  6. Dominic et al. (2014) Heart (British Cardiac Society) 100 (8):611-8 (PMID: 24449718)
  7. Friedrich et al. (2012) Human Molecular Genetics 21 (14):3237-54 (PMID: 22523091)
  8. B. Maron, M. Maron, & Semsarian (2012) J. Am. Coll. Cardiol. 60 (8):705-15 (PMID: 22796258)
  9. Frey, Luedde, & Katus (2012) Nature Reviews. Cardiology 9 (2):91-100 (PMID: 22027658)
  10. Ingles et al. (2015) Circ Cardiovasc Genet 8 (6):852-9 (PMID: 26671970)
  11. Hershberger et al. (2009) Journal Of Cardiac Failure 15 (2):83-97 (PMID: 19254666)
  12. Stenson et al. (2014) Human genetics 133 (1):1-9 (PMID: 24077912)
  13. Pan et al. (2012) Circulation. Cardiovascular Genetics 5 (6):602-10 (PMID: 23074333)
  14. Van Rijsingen et al. (2009) Netherlands Heart Journal : Monthly Journal Of The Netherlands Society Of Cardiology And The Netherlands Heart Foundation 17 (12):458- 63 (PMID: 20087448)
  15. Girolami et al. (2010) Journal Of The American College Of Cardiology 55 (14):1444-53 (PMID: 20359594)
  16. Gersh et al. (2011) Circulation 124 (24):2761-96 (PMID: 22068435)
  17. Olson et al. (2002) Circulation 105 (20):2337-40 (PMID: 12021217)

CREATE A CUSTOM PANEL

Test Details

  • Confirmation of clinical diagnosis in symptomatic patients
  • Genetic counseling and risk assessment of asymptomatic family members of a proband with a hereditary cardiovascular condition

Customizable Cardiology Panel

  • Next-Gen Sequencing
  • Exon Array CGH

Ordering

J779
4 weeks

Billing

Varies by gene
No
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Confirmation of a clinical diagnosis in symptomatic patients
  • Risk assessment of asymptomatic family members of a proband with DCM/LVNC
  • Differentiation of hereditary DCM from acquired (non-genetic) causes of DCM/LVNC
  • Recurrence risk calculation

Customizable Cardiology Panel

  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

J554C
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1, 81406x1, 81407x2
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM Number: {115200; 604169}: {04/21/2015; 09/04/2013}: World Wide Web URL: http://omim.org/
  2. Hershberger RE, Morales A. Dilated Cardiomyopathy Overview. 2007 Jul 27 [Updated 2013 May 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://w
  3. Callis et al. (2010) Expert review of molecular diagnostics 10(3):329-351 (PMID: 20370590)
  4. Bennett et al. (2016) Cardiology Research and Practice 2016:5172308 (PMID: 26881173)
  5. Rooms et al. (2015) Acta Cardiol 70 (6):625-31 (PMID: 26717209)
  6. Hershberger RE, Kushner JD, Parks SB. Dilated Cardiomyopathy Overview. GeneReviews. 2008. www.genetests.orgHunt et al. (2005) Circulation 112(12):e154-235 (PMID: 16160202)
  7. Herman et al. (2012) The New England Journal Of Medicine 366 (7):619-628 (PMID: 22335739)