1. bookTom 26 (2018): Zeszyt 4 (October 2018)
Informacje o czasopiśmie
License
Format
Czasopismo
eISSN
2284-5623
Pierwsze wydanie
08 Aug 2013
Częstotliwość wydawania
4 razy w roku
Języki
Angielski
access type Otwarty dostęp

The utility of molecular genetic techniques in craniosynostosis cases associated with intellectual disability

Data publikacji: 29 Oct 2018
Tom & Zeszyt: Tom 26 (2018) - Zeszyt 4 (October 2018)
Zakres stron: 471 - 477
Otrzymano: 29 Jul 2018
Przyjęty: 18 Sep 2018
Informacje o czasopiśmie
License
Format
Czasopismo
eISSN
2284-5623
Pierwsze wydanie
08 Aug 2013
Częstotliwość wydawania
4 razy w roku
Języki
Angielski
Abstract

Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR), providing information about the etiology of the genetic disorder. Muenke syndrome is produced by p.Pro250Arg mutation in FGFR3 gene with evidence of variable expressivity, representing 8% of the syndromic craniosynostoses.

Here, we present the identification of a p.Pro250Arg pathogenic mutation (c.749C>G) in the FGFR3 gene using Multiplex Ligation-dependent Probes Amplification (MLPA) analysis in conjunction with Sanger sequencing in a patient with craniosynostosis and mild intellectual disability. The MLPA analysis detected a reduced signal of the probe, at the site of the c.749C>G mutation, defined by the presence of one allele of C749>G mutation in the FGFR3 gene, exon 7. Sanger sequencing was performed for confirmation and identified heterozygous p.Pro250Arg pathogenic variant (c.749C>G) in exon 7 of the FGFR3.

In conclusion, we assessed the validity and clinical utility of the combined molecular genetic techniques, MLPA analysis, and Sanger sequencing, for craniosynostosis and intellectual disability, improving not only the diagnostic testing but also the genetic counseling and management of the disorder.

Keywords

1. Miller K, Twigg S, McGowan S, Phipps J, Fenwick A, Johnson D, et al. Diagnostic value of exome and whole genome sequencing in craniosynostosis. J Med Genet. 2017 Apr;54(4):260-8. DOI: 10.1136/jmedgenet-2016-10421510.1136/jmedgenet-2016-104215536606927884935Search in Google Scholar

2. Negura L, Negura A. Sanger sequencing of MMR genes in a one-plate system. Rev Romana Med Lab. 2018 Apr;26(2):153-63. DOI: 10.2478/rrlm-2018-000810.2478/rrlm-2018-0008Otwórz DOISearch in Google Scholar

3. Addissie, Yarnell C, Kruszk P, Muenke M. Muenke syndrome. Middle East J Med Genet. 2015 Jan;4:1-6. DOI: 10.1097/01.MXE.0000456629.07295.8e10.1097/01.MXE.0000456629.07295.8eOtwórz DOISearch in Google Scholar

4. Bellus G, Gaudenz K, Zackai E, Clarke L, Szabo J, Francomano C, et al. Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet. 1996 Oct;14(2):174–6. DOI: 10.1038/ng1096-17410.1038/ng1096-1748841188Otwórz DOISearch in Google Scholar

5. Muenke M, Gripp K, McDonald-McGinn D, Gaudenz K, Whitaker LA L, Bartlett S, et al. A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome. Am J Hum Genet. 1997 Mar;60(3):555–64.Search in Google Scholar

6. Boulet S, Rasmussen S, Honein M. A population-based study of craniosynostosis in metropolitan Atlanta, 1989–2003. AmJ Med Genet. 2008 Apr;146A(8):984–91. DOI: 10.1002/ajmg.a.3220810.1002/ajmg.a.3220818344207Search in Google Scholar

7. Kruszka P, Addissie Y, Yarnell C, Hadley D, Guillen Sacoto M, Platte P, et al. Muenke syndrome: An international multicenter natural history study. Am J Med Genet A. 2016 Apr;170A(4):918–29. DOI: 10.1002/ajmg.a.3752810.1002/ajmg.a.3752826740388Otwórz DOISearch in Google Scholar

8. Heuzé Y, Holmes G, Peter I, Richtsmeier J, Jabs E. Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses. Curr Genet Med Rep. 2014 Sep;2(3):135-45. DOI: 10.1007/s40142-014-0042-x10.1007/s40142-014-0042-x448914726146596Search in Google Scholar

9. Yu J, Park D, Yoon S. A Korean Family with the Muenke Syndrome. J Korean Med Sci. 2010 Jul;25(7):1086-9. DOI: 10.3346/jkms.2010.25.7.108610.3346/jkms.2010.25.7.1086289089020592905Otwórz DOISearch in Google Scholar

10. Yoon A, Pham B, Dipple K. Genetic Screening in Patients with Craniofacial Malformations. J Pediatr Genet. 2016 Dec;5(4):220-4. DOI: 10.1055/s-0036-159242310.1055/s-0036-1592423512389427895974Search in Google Scholar

11. Wilkie A, Johnson D, Wall S. Clinical Genetics of Craniosynostosis. Curr Opin Pediatr. 2017 Dec;29(6):622–8. DOI: 10.1097/MOP.000000000000054210.1097/MOP.0000000000000542568124928914635Search in Google Scholar

12. Lee E, Le T, Zhu Y, Elakis G, Turner A, Venselaar H, et al. A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations. Genet Med. 2017. DOI: 10.1038/gim.2017.21410.1038/gim.2017.21429215649Otwórz DOISearch in Google Scholar

13. Twigg S, Wilkie A. A Genetic-Pathophysiological Framework for Craniosynostosis. Am J Hum Genet. 2015 Sep;97(3):359-77. DOI: 10.1016/j.ajhg.2015.07.00610.1016/j.ajhg.2015.07.006456494126340332Otwórz DOISearch in Google Scholar

14. Nah H, Koyama E, Agochukwu N, Bart S, Muenke M. Phenotype profile of a genetic mouse model for Muenke syndrome. Childs Nerv Syst. 2012 Sep;28(9):1483-93. DOI: 10.1007/s00381-012-1778-910.1007/s00381-012-1778-9413198222872265Otwórz DOISearch in Google Scholar

15. Doherty E, Lacbawan F, Hadley D, Brewer C, Zalewski C, Kim H, et al. Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature. Am J Med Genet A. 2007 Dec;143A(24):3204-15. DOI: 10.1002/ajmg.a.3207810.1002/ajmg.a.3207818000976Otwórz DOISearch in Google Scholar

16. Escobar L, Hiett A, Marnocha A. Significant phenotypic variability of Muenke syndrome in identical twins. Am J Med Genet A. 2009 Jun;149A(6):1273-6. DOI: 10.1002/ajmg.a.3284110.1002/ajmg.a.3284119449410Otwórz DOISearch in Google Scholar

17. Solomon B, Muenke M. Muenke Syndrome. In Muenke M, Kress W, Collmann H, Solomon B, editors. Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment. Monogr Hum Genet. Basel: Karger; 2011:89-97. DOI: 10.1159/00031840710.1159/000318407Otwórz DOISearch in Google Scholar

18. Hamilton A, Tétreault M, Dyment D, Zou R, Kernohan K, Geraghty M, et al. Concordance between whole-exome sequencing and clinical Sanger sequencing: implications for patient care. Mol Genet Genomic Med. 2016 May;4(5):504-12. DOI: 10.1002/mgg3.22310.1002/mgg3.223502393527652278Otwórz DOISearch in Google Scholar

19. Hehr U. Molecular Genetic Testing of Patients with Craniosynostosis. In Muenke M, Kress W, Collmann H, Solomon B, editors. Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment. Monogr Hum Genet. Basel: Karger; 2011:177–83. DOI: 10.1159/00031842810.1159/000318428Otwórz DOISearch in Google Scholar

20. Phipps J, Skirton H. A Qualitative Study to Explore the Views and Attitudes towards Prenatal Testing in Adults Who Have Muenke Syndrome and their Partners. J Genet Couns. 2017 Oct;26(5):1130-42. DOI: 10.1007/s10897-017-0094-710.1007/s10897-017-0094-728332077Otwórz DOISearch in Google Scholar

21. Katsanis S, Katsanis N. Molecular genetic testing and the future of clinical genomics. Nat Rev Genet. 2013 Jun;14(6):415-26. DOI: 10.1038/nrg349310.1038/nrg3493446136423681062Otwórz DOISearch in Google Scholar

22. Sireteanu A, Popescu R, Braha E, Bujoran C, Butnariu L, Caba L, et al. Detection of chromosomal imbalances using combined MLPA kits in patients with syndromic intellectual disability. Rev Romana Med Lab. 2014 Jun;22(2):157-64. DOI: 10.2478/rrlm-2014-001910.2478/rrlm-2014-0019Otwórz DOISearch in Google Scholar

Polecane artykuły z Trend MD

Zaplanuj zdalną konferencję ze Sciendo