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Szabo A, Czako M, Hadzsiev K, et al. Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype. Mol Cytogenet. 2015;8:41doi: 10.1186/s13039-015-0137-4.
Szabo, A., Czako, M., Hadzsiev, K., Duga, B., Komlosi, K., & Melegh, B. (2015). Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype. Molecular cytogenetics, 841. https://doi.org/10.1186/s13039-015-0137-4
Szabo, Andras, et al. "Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype." Molecular cytogenetics vol. 8 (2015): 41. doi: https://doi.org/10.1186/s13039-015-0137-4
Szabo A, Czako M, Hadzsiev K, Duga B, Komlosi K, Melegh B. Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype. Mol Cytogenet. 2015 Jun 25;8:41. doi: 10.1186/s13039-015-0137-4. eCollection 2015. PMID: 26110020; PMCID: PMC4479342.
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Mol Cytogenet. 2015 Jun 25;8:41. doi: 10.1186/s13039-015-0137-4. eCollection 2015.

Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype.

Molecular cytogenetics

Andras Szabo, Marta Czako, Kinga Hadzsiev, Balazs Duga, Katalin Komlosi, Bela Melegh

Affiliations

  1. Department of Medical Genetics, University of Pecs, Szigeti 12, H-7624 Pecs, Hungary ; Szentagothai Research Centre, Ifjusag 20, H-7624 Pecs, Hungary.

PMID: 26110020 PMCID: PMC4479342 DOI: 10.1186/s13039-015-0137-4

Abstract

BACKGROUND: Large amounts of low copy number repeats in the 15q11.2q13.3 chromosomal region increase the possibility of misalignments and unequal crossover during meiosis in this region, leading to deletions, duplications, triplications and supernumerary chromosomes. Most of the reported cases with epilepsy, autism and Prader-Willi/Angelman syndrome are in association with rearrangements of the proximal long arm of chromosome 15.

RESULTS: Here we report the first two unrelated Hungarian patients with the same epileptic and dysmorphic features, who were investigated by array comparative genomic hybridization (array CGH). By G-banded karyotype followed by FISH and array CGH we could detect partial tetrasomy of the 15q11.2q13.3 chromosomal region, supporting proximal 15q duplication syndrome. Findings of the array CGH gave fully explanation of the phenotypic features of these patients, including epileptic seizures, delayed development, hyperactivity and craniofacial dysmorphic signs. Besides the described features of isodicentric (15) (idic(15)) syndrome Patient 1. suffered from bigeminic extrasystoles and had postnatal growth retardation, which had been published only in a few articles.

CONCLUSIONS: Dosage effect of some genes in the concerned genomic region is known, but several genes have no evidence to have dosage dependence. Our results expanded the previous literature data. We assume dosage dependence in the case of CHRNA7 and OTUD7A, which might be involved in growth regulation. On the other hand increased dosage of the KLF13 gene seems to have no direct causal relationship with heart morphology. The genomic environment of the affected genes may be responsible for the observed phenotype.

Keywords: 15q duplication syndrome; Array CGH; Dysmorphism; Epilepsy; Supernumerary chromosome

References

  1. Arq Bras Cardiol. 2015 Jan;104(1):24-31 - PubMed
  2. Clin Genet. 2005 Dec;68(6):513-9 - PubMed
  3. Hum Mol Genet. 2009 Oct 15;18(20):3805-21 - PubMed
  4. Am J Med Genet A. 2013 Oct;161A(10):2582-7 - PubMed
  5. Clin Genet. 1991 Sep;40(3):233-6 - PubMed
  6. Psychiatr Genet. 2015 Apr;25(2):59-70 - PubMed
  7. Clin Genet. 2010 Aug;78(2):149-61 - PubMed
  8. Am J Med Genet. 2001 Nov 1;103(4):289-94 - PubMed
  9. Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R189-96 - PubMed
  10. Am J Hum Genet. 2004 Aug;75(2):267-81 - PubMed
  11. EMBO J. 2006 Nov 1;25(21):5201-13 - PubMed
  12. Nature. 2003 Jan 23;421(6921):384-8 - PubMed
  13. Am J Med Genet. 1998 Sep 7;81(5):428-33 - PubMed
  14. Prenat Diagn. 1999 Aug;19(8):721-6 - PubMed
  15. J Med Genet. 2009 Feb;46(2):86-93 - PubMed
  16. BMC Med Genet. 2013 Jan 15;14:9 - PubMed
  17. Am J Hum Genet. 1994 Oct;55(4):753-9 - PubMed
  18. Genomics. 1994 Jan 1;19(1):157-60 - PubMed
  19. Nat Genet. 2008 Mar;40(3):322-8 - PubMed
  20. Am J Hum Genet. 2003 Nov;73(5):1061-72 - PubMed
  21. Eur J Med Genet. 2005 Apr-Jun;48(2):175-81 - PubMed
  22. Trends Plant Sci. 1999 Nov;4(11):446-452 - PubMed
  23. Am J Med Genet. 1997 May 2;70(1):37-42 - PubMed
  24. Am J Med Genet. 1991 Jan;38(1):74-9 - PubMed
  25. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9138-42 - PubMed
  26. Eur J Hum Genet. 2014 Sep;22(9):1071-6 - PubMed
  27. Nat Genet. 1994 Jun;7(2 Spec No):246-339 - PubMed
  28. Chromosoma. 1970;30(2):215-27 - PubMed
  29. Biochem Biophys Res Commun. 2006 Jun 2;344(2):531-9 - PubMed
  30. Hum Genet. 2004 Jul;115(2):104-11 - PubMed
  31. Am J Med Genet A. 2006 Mar 1;140(5):434-41 - PubMed
  32. Clin Genet. 2004 Mar;65(3):242-3 - PubMed
  33. PLoS Genet. 2007 Dec 28;3(12):e235 - PubMed
  34. J Med Genet. 2009 Aug;46(8):511-23 - PubMed
  35. Drugs. 1991 Jun;41(6):889-926 - PubMed
  36. Drugs. 1994 Feb;47(2):332-72 - PubMed
  37. Orphanet J Rare Dis. 2008 Nov 19;3:30 - PubMed
  38. Nature. 1989 Nov 16;342(6247):281-5 - PubMed
  39. Cell Cycle. 2007 Jan 15;6(2):117-21 - PubMed
  40. Med Wieku Rozwoj. 2012 Jul-Sep;16(3):175-82 - PubMed
  41. Am J Med Genet. 2002 Sep 1;111(4):440-2 - PubMed
  42. Science. 1992 Oct 30;258(5083):818-21 - PubMed
  43. Balkan J Med Genet. 2012 Dec;15(2):15-22 - PubMed
  44. Am J Med Genet C Semin Med Genet. 2010 Nov 15;154C(4):448-55 - PubMed

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