Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2019 Volume 20 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2019 Volume 20 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients

  • Authors:
    • Haibei Li
    • Haiqi Yang
    • Nan Lv
    • Caiyun Ma
    • Jingjie Li
    • Qing Shang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450053, P.R. China, Aegicare (Shenzhen) Technology Co., Ltd., Shenzhen, Guangdong 518060, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1178-1186
    |
    Published online on: June 5, 2019
       https://doi.org/10.3892/mmr.2019.10339
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Angelman syndrome (AS) is a congenital neuro­developmental disorder typically occurring due to functional defects of the UBE3A gene caused by uniparental disomy (UPD), translocation or single gene mutation. UBE3A gene exhibits imprinting expression, and only maternal inherited alleles express functional UBE3A protein in the brain. The common method to diagnose AS is single nucleotide polymorphism array or methylation‑specific multiplex ligation‑dependent probe amplification (MS‑MLPA). In recent years, whole exome sequencing (WES) has been increasingly used in the genetic diagnosis of a variety of indications, exhibiting great advantages as a comprehensive and unbiased testing method. In the present study, the cases of two unrelated patients with Robertsonian‑like translocation in chromosome 15, namely 45,XX,der(15;15)(q10;q10) and 45,XY,der(15;15)(q10;q10), are reported. The first case was diagnosed with AS by WES and validated by Sanger sequencing. In contrast to 42.84%  homozygous variants on all chromosomes, 92.69%  homozygosity variants were observed on chromosome 15. A homozygous stretch identifier was applied and identified a homozygous region across the entire chromosome 15. Sanger sequencing was used to further determine the subtype and confirm that two homozygous variants on chromosome 15 with low allele frequency (<0.01) were derived only from the father and not from the mother, thereby indicating a paternal UPD case, classified as isodisomy. MS‑MLPA results of the other AS patient with the same karyotype indicated that he had a high possibility of paternal UPD at chromosome 15. Taken together, the current study suggested the potential application of WES in detecting and facilitating the diagnosis of UPD.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Kishino T, Lalande M and Wagstaff J: UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 15:70–73. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Rougeulle C, Glatt H and Lalande M: The Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain. Nat Genet. 17:14–15. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Sato M: Early origin and evolution of the angelman syndrome ubiquitin ligase gene Ube3a. Front Cell Neurosci. 11:622017. View Article : Google Scholar : PubMed/NCBI

4 

Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Griffith EC, Waldon Z, Maehr R, et al: The angelman syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell. 140:704–716. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Clayton-Smith J and Laan L: Angelman syndrome: A review of the clinical and genetic aspects. J Med Genet. 40:87–95. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Fridman C and Koiffmann CP: Origin of uniparental disomy 15 in patients with Prader-Willi or Angelman syndrome. Am J Med Genet. 94:249–253. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Knoll JH, Glatt KA, Nicholls RD, Malcolm S and Lalande M: Chromosome 15 uniparental disomy is not frequent in Angelman syndrome. Am J Hum Genet. 48:16–21. 1991.PubMed/NCBI

8 

Siegel DH and Slavotinek A: Uniparental disomy. Pediatr Dermatol. 22:482–487. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Shaffer LG: Risk estimates for uniparental disomy following prenatal detection of a nonhomologous Robertsonian translocation. Prenat Diagn. 26:303–307. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Poyatos D, Guitart M, Gabau E, Brun C, Mila M, Vaquerizo J and Coll MD: Severe phenotype in Angelman syndrome resulting from paternal isochromosome 15. J Med Genet. 39:E42002. View Article : Google Scholar : PubMed/NCBI

11 

Bis DM, Schule R, Reichbauer J, Synofzik M, Rattay TW, Soehn A, de Jonghe P, Schöls L and Züchner S: Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias. Mol Genet Genomic Med. 5:280–286. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Carmichael H, Shen Y, Nguyen TT, Hirschhorn JN and Dauber A: Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype. Clin Genet. 84:213–222. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Kurth I, Baumgartner M, Schabhuttl M, Tomni C, Windhager R, Strom TM, Wieland T, Gremel K and Auer-Grumbach M: Whole exome sequencing in congenital pain insensitivity identifies a novel causative intronic NTRK1-mutation due to uniparental disomy. Am J Med Genet B Neuropsychiatr Genet. 171:875–878. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Gormez Z, Bakir-Gungor B and Sagiroglu MS: HomSI: A homozygous stretch identifier from next-generation sequencing data. Bioinformatics. 30:445–447. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Li H and Durbin R: Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 25:1754–1760. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G and Durbin R; 1000 Genome Project Data Processing Subgroup, : The sequence Alignment/Map format and SAMtools. Bioinformatics. 25:2078–2079. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Talevich E, Shain AH, Botton T and Bastian BC: CNVkit: Genome-Wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput Biol. 12:e10048732016. View Article : Google Scholar : PubMed/NCBI

18 

McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P and Cunningham F: The ensembl variant effect predictor. Genome Biol. 17:1222016. View Article : Google Scholar : PubMed/NCBI

19 

Ng PC and Henikoff S: SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 31:3812–3814. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS and Sunyaev SR: A method and server for predicting damaging missense mutations. Nat Methods. 7:248–249. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Stenson PD, Mort M, Ball EV, Shaw K, Phillips A and Cooper DN: The human gene mutation database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet. 133:1–9. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, Handsaker RE, Lunter G, Marth GT, Sherry ST, et al: The variant call format and VCFtools. Bioinformatics. 27:2156–2158. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Glenn CC, Driscoll DJ, Yang TP and Nicholls RD: Genomic imprinting: Potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes. Mol Hum Reprod. 3:321–332. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Tonk V, Schultz RA, Christian SL, Kubota T, Ledbetter DH and Wilson GN: Robertsonian (15q;15q) translocation in a child with Angelman syndrome: Evidence of uniparental disomy. Am J Med Genet. 66:426–428. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Freeman SB, May KM, Pettay D, Fernhoff PM and Hassold TJ: Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome. Am J Med Genet. 45:625–630. 1993. View Article : Google Scholar : PubMed/NCBI

26 

Fridman C, Varela MC, Nicholls RD and Koiffmann CP: Unusual clinical features in an Angelman syndrome patient with uniparental disomy due to a translocation 15q15q. Clin Genet. 54:303–308. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Ramsden S, Gaunt L, Seres-Santamaria A and Clayton-Smith J: A case of Angelman syndrome arising as a result of a de novo Robertsonian translocation. Acta Genet Med Gemellol (Roma). 45:255–261. 1996. View Article : Google Scholar : PubMed/NCBI

28 

Horvath E, Horvath Z, Isaszegi D, Gergev G, Nagy N, Szabó J, Sztriha L, Széll M and Endreffy E: Early detection of Angelman syndrome resulting from de novo paternal isodisomic 15q UPD and review of comparable cases. Mol Cytogenet. 6:352013. View Article : Google Scholar : PubMed/NCBI

29 

Robinson WP, Christian SL, Kuchinka BD, Peñaherrera MS, Das S, Schuffenhauer S, Malcolm S, Schinzel AA, Hassold TJ and Ledbetter DH: Somatic segregation errors predominantly contribute to the gain or loss of a paternal chromosome leading to uniparental disomy for chromosome 15. Clin Genet. 57:349–358. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Smith A, Robson L and Buchholz B: Normal growth in Angelman syndrome due to paternal UPD. Clin Genet. 53:223–225. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Varela MC, Kok F, Otto PA and Koiffmann CP: Phenotypic variability in Angelman syndrome: Comparison among different deletion classes and between deletion and UPD subjects. Eur J Hum Genet. 12:987–992. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA and Wagstaff J: Angelman syndrome 2005: Updated consensus for diagnostic criteria. Am J Med Genet A. 140:413–418. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Zhu X, Petrovski S, Xie P, Ruzzo EK, Lu YF, McSweeney KM, Ben-Zeev B, Nissenkorn A, Anikster Y, Oz-Levi D, et al: Whole-exome sequencing in undiagnosed genetic diseases: Interpreting 119 trios. Genet Med. 17:774–781. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Stranneheim H and Wedell A: Exome and genome sequencing: A revolution for the discovery and diagnosis of monogenic disorders. J Intern Med. 279:3–15. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Pfundt R, Del Rosario M, Vissers LELM, Kwint MP, Janssen IM, de Leeuw N, Yntema HG, Nelen MR, Lugtenberg D, Kamsteeg EJ, et al: Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders. Genet Med. 19:667–675. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li H, Yang H, Lv N, Ma C, Li J and Shang Q: Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients. Mol Med Rep 20: 1178-1186, 2019.
APA
Li, H., Yang, H., Lv, N., Ma, C., Li, J., & Shang, Q. (2019). Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients. Molecular Medicine Reports, 20, 1178-1186. https://doi.org/10.3892/mmr.2019.10339
MLA
Li, H., Yang, H., Lv, N., Ma, C., Li, J., Shang, Q."Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients". Molecular Medicine Reports 20.2 (2019): 1178-1186.
Chicago
Li, H., Yang, H., Lv, N., Ma, C., Li, J., Shang, Q."Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients". Molecular Medicine Reports 20, no. 2 (2019): 1178-1186. https://doi.org/10.3892/mmr.2019.10339
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Yang H, Lv N, Ma C, Li J and Shang Q: Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients. Mol Med Rep 20: 1178-1186, 2019.
APA
Li, H., Yang, H., Lv, N., Ma, C., Li, J., & Shang, Q. (2019). Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients. Molecular Medicine Reports, 20, 1178-1186. https://doi.org/10.3892/mmr.2019.10339
MLA
Li, H., Yang, H., Lv, N., Ma, C., Li, J., Shang, Q."Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients". Molecular Medicine Reports 20.2 (2019): 1178-1186.
Chicago
Li, H., Yang, H., Lv, N., Ma, C., Li, J., Shang, Q."Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients". Molecular Medicine Reports 20, no. 2 (2019): 1178-1186. https://doi.org/10.3892/mmr.2019.10339
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team