Pearson Syndrome

Forms and Documents

Test Details

  • Molecular confirmation of a clinical diagnosis
  • Testing of patients suspected of having a mitochondrial disorder

65 confirmed disease-causing mtDNA point variants (see list in Test Info Sheet) and large scale deletion analysis of the mitochondrial genome (including LHON [20 mutations], MELAS [16 mutations], LS/NARP [22 mutations], MIHL/MIDM [10 mutations)] MERRF [6 mutations], KSS, CPEO, Pearson syndrome, etc.)

  • Next-Gen Sequencing

Ordering

704
3-4 weeks
Tissue Biopsy (>50 mg Muscle or Liver-Flash Frozen)
2-5 mL Blood - Lavender Top Tube|Oral Rinse (30-40 mL)

Billing

81465x1, 81401x5
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Longo, N. (2003) Neurol Clin N Am 21:817-831.
  2. Majamaa et al., (1998) Am J Hum Genet 63:447-454.
  3. Goto et al., (1991) Biochim Biophys Acta 1097:238-40.
  4. Mackey et al., (1996) Am J Hum Genet 59:481-485.
  5. Taylor et al., (2003) J Am Coll Cardiol 41:1786-96.
  6. DiMauro, S. Gene Reviews (2005) MERRF.
  7. Thorburn, D. Gene Reviews (2006) Mitochondrial DNA-Associated Leigh Syndrome and NARP.
  8. DiMauro, S. Gene Reviews (2005) MELAS.
  9. Yu-Wai-Man, P and Chinnery, P. Gene Reviews (2008) Leber Hereditary Optic Neuropathy.
  10. Macmillan et al., (1998) Neurology 50:417-22.
  11. Crispim et al., (2008) Arq Bras Endocrinol Metab 52:1228-1235.
  12. Zhu et al., (2009) Acta Biochim Biophys Sin 41:179-187.
  13. Chinnery, P. Gene Reviews (2006) Mitochondrial Disorders Overview.
  14. Bennett S.(2004) Pharmacogenomics 5:433-8
  15. MITOMAP: A Human Mitochondrial Genome Database. http://www.mitomap.org, 2008.
  16. Achilli et al., (2012) PLoS One 7:e42242.
  17. Pulkes et al., (1999) Ann Neurol 46:916-9.
  18. DiMaruo, S. and Hirano, M. (Updated [May 3, 2011]). Mitochondrial DNA Deletion Syndromes In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at http://w
  19. Jeppesen TD,et al. (2003) Ann Neurol 54(1):86-92.
  20. Moraes et al., (1989) N Engl J Med 18:1293-9.
  21. Chinault et al., Genet Med (2009)11:518-526
  22. Uusimaa et al., (2000) Pediatrics 105:598-603
  23. Remes et al., (2005) Neurology 64:976-981
  24. Darin et al., (2001) Ann Neurol 49:377-383
  25. Wong, L. and Senadheera, D. (1997) Clin Chem 43:1857-1861
  26. Jaksch et al., (2001) J Med Genet 38:665-673

Forms and Documents

Test Details

  • Molecular confirmation of a clinical diagnosis
  • Testing of patients suspected of having a mitochondrial disorder
  • Next-Gen Sequencing

Ordering

554
4 weeks
Tissue Biopsy (>50 mg Muscle or Liver-Flash Frozen)
2-5 mL Blood - Lavender Top Tube|Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81460x1, 81465x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Oliveira et al., (2005) Dev Med Child Neurol 47:185-189.
  2. Zhu et al., (2009) Acta Biochim Biophys Sin 41:179-187
  3. Chinnery, P. Gene Reviews (2006) Mitochondrial Disorders Overview.
  4. Tarnopolsky, M and Raha S. (2005) Med Sci Sports Exerc 37:2086-93.
  5. van Adel, B. and Tarnopolsky, M. (2009) J Clin Neuromusc Dis 10:97-121.
  6. Longo, N. (2003) Neurol Clin N Am 21:817- 831.
  7. Bennett S.(2004) Pharmacogenomics 5:433-8.
  8. Chinnery, P. Gene Reviews (2006) Mitochondrial Disorders Overview.
  9. Koenig MK. (2008) Pediatr Neurol, 38:305-313.
  10. Zeviani1 and Di Donato. (2004) Brain, 127: 2153–2172.

Forms and Documents

Test Details

  • Molecular confirmation of a clinical diagnosis
  • Testing of patients suspected of having a mitochondrial disorder
  • Exon Array CGH

Ordering

444
3-4 weeks
Tissue Biopsy (>50 mg Muscle or Liver-Flash Frozen)
2-5 mL Blood - Lavender Top Tube

Billing

81465x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Chinault et al., Genet Med (2009)11:518-526
  2. Uusimaa et al., (2000) Pediatrics 105:598-603
  3. Wong, L. and Senadheera, D. (1997) Clin Chem 43:1857-1861
  4. Darin et al., (2001) Ann Neurol 49:377-383
  5. Remes et al., (2005) Neurology 64:976-981
  6. Jaksch et al., (2001) J Med Genet 38:665-673
  7. Sternberg et al., (2001) Brain 124:984-994
  8. Crispim et al., (2008) Arq Bras Endocrinol Metab 52:1228-1235
  9. Yu-Wai-Man, P and Chinnery, P. Gene Reviews (2008) Leber Hereditary Optic Neuropathy
  10. DiMauro, S. Gene Reviews (2005) MELAS
  11. Taylor et al., (2003) J Am Coll Cardiol 41:1786-96
  12. Thorburn, D. Gene Reviews (2006) Mitochondrial DNAAssociated Leigh Syndrome and NARP
  13. DiMauro, S. Gene Reviews (2005) MERRF
  14. Macmillan et al., (1998) Neurology 50:417-22
  15. Mackey et al., (1996) Am J Hum Genet 59:481-485
  16. Majamaa et al., (1998) Am J Hum Genet 63:447-454
  17. Goto et al., (1991) Biochim Biophys Acta 1097:238-40
  18. DiMaruo, S. Gene Reviews (2007) Mitochondrial DNA Deletion Syndromes
  19. Harding, A. and Hammans, S. (1992) J Inher Metab Dis 15:480-486
  20. Moraes et al., (1989) N Engl J Med 18:1293-9
  21. Longo, N. (2003) Neurol Clin N Am 21:817- 831
  22. van Adel, B. and Tarnopolsky, M. (2009) J Clin Neuromusc Dis 10:97-121
  23. Tarnopolsky, M and Raha S. (2005) Med Sci Sports Exerc 37:2086-93
  24. Chinnery, P. Gene Reviews (2006) Mitochondrial Disorders Overview
  25. Zhu et al., (2009) Acta Biochim Biophys Sin 41:179-187
  26. Oliveira et al., (2005) Dev Med Child Neurol 47:185-189

Forms and Documents

Test Details

ABCB7, ALAS2, GLRX5, PUS1, SLC19A2, SLC25A38, TRNT1, YARS2
  • Mitochondrial genome large deletion testing
  • Confirmation of a clinical diagnosis
  • To assist in determining the most appropriate therapy, as the response to specific therapeutic modalities depends on the diagnosis
  • Targeted testing for a known familial variant
  • Prenatal diagnosis for known familial variants in nuclear genes in at-risk pregnancies
  • Genetic counseling
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

938
4 weeks
2-5 mL Blood - Lavender Top Tube

Billing

81465x1, 81479x8
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. OMIM, Online Mendelian Inheritance in Man, (TM). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), http://www.ncbi.nlm.n
  2. Bergmann AK et al. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatric Blood & Cancer. 2010 Feb 54(2):273-8. (PMID:19731322)
  3. Ohba R et al. Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS). Annals Of Hematology. 2013 Jan 92(1):1-9. (PMID:22983749)
  4. Bekri S, D’Hooghe M, Vermeersch P. X-Linked Sideroblastic Anemia and Ataxia. 2006 Mar 1 [Updated 2014 Apr 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Availab
  5. Aivado M et al. X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood Cells, Molecules & Diseases. 37(1):40-5. (PMID: 16735131)
  6. Guernsey DL et al. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nature Genetics. 2009 Jun 41(6):651-3. (PMID: 19412178)
  7. Rouault TA and Tong WH. Iron-sulfur cluster biogenesis and human disease. Trends In Genetics : Tig. 2008 Aug 24(8):398-407. (PMID:18606475)
  8. Ye H et al. Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. The Journal Of Clinical Investigation. 2010 May 120(5):1749-61. (PMID:20364084)
  9. Bykhovskaya Y et al. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). American Journal Of Human Genetics. 2004 Jun 74(6):1303-8. (PMID: 15108122)
  10. Bergmann AK et al. Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update. The Journal Of Pediatrics. 2009 Dec 155(6):888-892. (PMID: 19643445)
  11. Chakraborty PK et al. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood. 2014 Oct 30 124(18):2867-71. (PMID: 25193871)
  12. Wiseman DH et al. A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood. 2013 Jul 4 122(1):112-23. (PMID: 23553769)
  13. Riley LG et al. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. American Journal Of Human Genetics. 2010 87(1):52-9. (PMID: 20598274)
  14. Riley LG et al. Phenotypic variability and identification of novel YARS2 mutations in YARS2 mitochondrial myopathy, lactic acidosis and sideroblastic anaemia. Orphanet Journal Of Rare Diseases. 2013 8:193. (PMID: 24344687)
  15. DiMauro S, Hirano M. Mitochondrial DNA Deletion Syndromes. 2003 Dec 17 [Updated 2011 May 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://w
  16. Bekri S et al. Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Blood. 2000 96(9):3256-64. (PMID: 11050011)
  17. D\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'Hooghe M et al. X-linked sideroblastic anemia and ataxia: a new family with identification of a fourth ABCB7 gene mutation. European Journal Of Paediatric Neurology : Ejpn : Official Journal Of The European Paediatric Neur
  18. Maguire A et al. X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L. British Journal Of Haematology. 2001 Dec 115(4):910-7. (PMID: 11843825)
  19. Bishop DF et al. X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the ?-subunit of succinyl-CoA synthetase (SUCLA2). The Journal Of Biological Chemistry. 2012 287(34):28943-55. (PMID:22740690)
  20. Campagna DR et al. X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations. American Journal Of Hematology. 2014 Mar 89(3):315-9. (PMID:24166784)
  21. Kaneko K et al. Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia. Haematologica. 2014 Feb 99(2):252-61. (PMID:23935018)
  22. . Stenson et al. (2014) The Human Gene Mutation Database (HGMD®) Human genetics 133(1):1-9 (PMID: 24077912)
  23. Kannengiesser C et al. Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia. Haematologica. 2011 Jun 96(6):808-13. (PMID:21393332)
  24. . Fernandez-Vizarra E et al. Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA). Journal Of Medical Genetics. 2007 Mar 44(3):173-80. (PMID: 17056637)
  25. Oishi K, Diaz GA. Thiamine-Responsive Megaloblastic Anemia Syndrome. 2003 Oct 24 [Updated 2014 Nov 20]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available fro
  26. Labay V et al. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nature Genetics. 1999 Jul 22(3):300-4. (PMID: 10391221)
  27. Scharfe C et al. A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. Journal Of Medical Genetics. 2000 Sep 37(9):669-73. (PMID: 10978358)
  28. Shahni R et al. A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations. American Journal Of Medical Genetics. Part A. 2013 161(9):2334-8. (PMID:23918765)