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Baas M, Burger EB, van den Ouweland AM, et al. Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes. J Med Genet. 2020;58(6):362-368doi: 10.1136/jmedgenet-2020-106948.
Baas, M., Burger, E. B., van den Ouweland, A. M., Hovius, S. E., de Klein, A., van Nieuwenhoven, C. A., & Galjaard, R. J. H. (2021). Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes. Journal of medical genetics, 58(6), 362-368. https://doi.org/10.1136/jmedgenet-2020-106948
Baas, Martijn, et al. "Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes." Journal of medical genetics vol. 58,6 (2021): 362-368. doi: https://doi.org/10.1136/jmedgenet-2020-106948
Baas M, Burger EB, van den Ouweland AM, Hovius SE, de Klein A, van Nieuwenhoven CA, Galjaard RJH. Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes. J Med Genet. 2021 Jun;58(6):362-368. doi: 10.1136/jmedgenet-2020-106948. Epub 2020 Jun 26. PMID: 32591344; PMCID: PMC8142428.
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J Med Genet. 2021 Jun;58(6):362-368. doi: 10.1136/jmedgenet-2020-106948. Epub 2020 Jun 26.

Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes.

Journal of medical genetics

Martijn Baas, Elise Bette Burger, Ans Mw van den Ouweland, Steven Er Hovius, Annelies de Klein, Christianne A van Nieuwenhoven, Robert Jan H Galjaard

Affiliations

  1. Plastic, Reconstructive and Hand Surgery, Erasmus MC, Rotterdam, The Netherlands [email protected].
  2. Plastic, Reconstructive and Hand Surgery, Erasmus MC, Rotterdam, The Netherlands.
  3. Clinical Genetics, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands.
  4. Plastic, Reconstructive and Hand Surgery, Radboud University Nijmegen, Nijmegen, Gelderland, The Netherlands.
  5. Hand and Wrist Centre, Xpert Clinic, Eindhoven, The Netherlands.

PMID: 32591344 PMCID: PMC8142428 DOI: 10.1136/jmedgenet-2020-106948

Abstract

INTRODUCTION: Pathogenic DNA variants in the GLI-Kruppel family member 3 (

METHODS: Both local and published cases were included for analysis. The presence of individual limb phenotypes was dichotomised and an exploratory LCA was performed. Distribution of phenotypes and genotypes over the classes were explored and subsequently the key predictors of latent class membership were correlated to the different clustered genotypes.

RESULTS: 297 cases were identified with 127 different variants in the

CONCLUSION: There are two distinct phenotypes within the GLI3-mediated polydactyly population: anteriorly and posteriorly orientated. Variants that likely produce haploinsufficiency are associated with anterior phenotypes. Posterior phenotypes are associated with truncating variants in the activator domain. Patients with these truncating variants have a greater risk for corpus callosum anomalies.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Keywords: clinical genetics; developmental; genetic screening/counselling; molecular genetics

Conflict of interest statement

Competing interests: None declared.

References

  1. Am J Med Genet A. 2003 Jul 1;120A(1):49-58 - PubMed
  2. PLoS One. 2009 Oct 15;4(10):e7471 - PubMed
  3. J Neurosurg. 2007 Dec;107(6 Suppl):495-9 - PubMed
  4. Hum Mol Genet. 2017 Dec 1;26(23):4556-4571 - PubMed
  5. Eur J Hum Genet. 2011 Jul;19(7):757-62 - PubMed
  6. Methods Mol Biol. 2017;1492:243-251 - PubMed
  7. Hum Genet. 2004 Mar;114(4):403 - PubMed
  8. Front Cell Dev Biol. 2017 Feb 28;5:14 - PubMed
  9. Meta Gene. 2014 Nov 25;2:880-7 - PubMed
  10. J Med Genet. 2006 Jun;43(6):465-9 - PubMed
  11. Am J Med Genet A. 2013 Nov;161A(11):2734-40 - PubMed
  12. Congenit Anom (Kyoto). 2016 Mar;56(2):94-7 - PubMed
  13. Clin Genet. 2012 Nov;82(5):502-4 - PubMed
  14. Hum Mutat. 2003 Jun;21(6):577-81 - PubMed
  15. Hum Mol Genet. 1999 Sep;8(9):1769-77 - PubMed
  16. Am J Med Genet A. 2017 Dec;173(12):3221-3225 - PubMed
  17. Mol Cell Biol. 2006 Dec;26(23):8667-82 - PubMed
  18. Mol Cell Biol. 1990 Oct;10(10):5408-15 - PubMed
  19. Genet Test Mol Biomarkers. 2018 Sep;22(9):577-581 - PubMed
  20. Am J Med Genet A. 2013 Jun;161A(6):1394-400 - PubMed
  21. Dev Biol. 2015 Oct 1;406(1):92-103 - PubMed
  22. Prenat Diagn. 2015 Feb;35(2):203-5 - PubMed
  23. Am J Hum Genet. 1999 Sep;65(3):645-55 - PubMed
  24. Dev Biol. 2009 Apr 15;328(2):506-16 - PubMed
  25. J Med Genet. 2002 Nov;39(11):804-6 - PubMed
  26. Am J Med Genet A. 2003 Dec 15;123A(3):236-42 - PubMed
  27. Cell. 2000 Feb 18;100(4):423-34 - PubMed
  28. Eur J Pediatr. 2013 Aug;172(8):1131-5 - PubMed
  29. Am J Med Genet A. 2007 Dec 15;143A(24):3150-60 - PubMed
  30. Am J Med Genet A. 2010 Jul;152A(7):1654-60 - PubMed
  31. Clin Chim Acta. 2014 Jun 10;433:195-9 - PubMed
  32. J Hum Genet. 2016 Oct;61(10):907-910 - PubMed
  33. Clin Genet. 2017 Nov;92(5):457-466 - PubMed
  34. Hum Mutat. 2010 Oct;31(10):1142-54 - PubMed
  35. Eur J Hum Genet. 2015 Jan;23(1):92-102 - PubMed
  36. Ann Plast Surg. 2019 May;82(5):570-573 - PubMed
  37. J Appl Genet. 2012 Nov;53(4):415-22 - PubMed
  38. J Biol Chem. 1999 Mar 19;274(12):8143-52 - PubMed
  39. Am J Med Genet. 1983 Nov;16(3):313-21 - PubMed
  40. Nat Genet. 1997 Nov;17(3):269-71 - PubMed
  41. J Med Genet. 2009 Nov;46(11):730-5 - PubMed
  42. Struct Equ Modeling. 2007;14(4):671-694 - PubMed
  43. Am J Hum Genet. 2005 Apr;76(4):609-22 - PubMed
  44. Nat Genet. 1997 Mar;15(3):266-8 - PubMed
  45. Clin Chim Acta. 2011 May 12;412(11-12):1012-7 - PubMed

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