Cargando…
Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features
BACKGROUND: Loss of expression of imprinted genes in the 15q11.2-q13 region is known to cause either Prader-Willi syndrome (PWS) or Angelman syndrome (AS), depending on the parent of origin. In some patients (1 % in PWS and 2–4 % in AS), the disease is due to aberrant imprinting or gene silencing, o...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802915/ https://www.ncbi.nlm.nih.gov/pubmed/27006693 http://dx.doi.org/10.1186/s13039-016-0233-0 |
_version_ | 1782422813669326848 |
---|---|
author | Aypar, Umut Hoppman, Nicole L. Thorland, Erik C. Dawson, D. Brian |
author_facet | Aypar, Umut Hoppman, Nicole L. Thorland, Erik C. Dawson, D. Brian |
author_sort | Aypar, Umut |
collection | PubMed |
description | BACKGROUND: Loss of expression of imprinted genes in the 15q11.2-q13 region is known to cause either Prader-Willi syndrome (PWS) or Angelman syndrome (AS), depending on the parent of origin. In some patients (1 % in PWS and 2–4 % in AS), the disease is due to aberrant imprinting or gene silencing, or both. RESULTS: We report here a 4-year-old boy on whom a chromosomal microarray (CMA) was performed due to mild hand tremors, mild developmental delays, and clumsiness. CMA revealed absence of heterozygosity (AOH) spanning the entire chromosome 15, suggesting uniparental isodisomy 15. The patient had no definitive phenotypic features of PWS or AS. Methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) was performed to determine the parent of origin of the uniparental disomy (UPD) by examining methylation status at maternally imprinted sites. Interestingly, our patient had a mosaic methylation pattern. We identified nine additional previously tested patients with a similar mosaic methylation pattern. CMA was performed on these individuals retrospectively to test whether patients with mosaic methylation are more likely to have UPD of chromosome 15. Of the nine patients, only one had regions of AOH on chromosome 15; however, this patient had numerous regions of AOH on multiple chromosomes suggestive of consanguinity. CONCLUSION: The patients with mosaic methylation had milder or atypical features of AS, and the majority also had some features characteristic of PWS. We suggest that quantitative methylation analysis be performed for cases of atypical PWS or AS. It is also important to follow up with methylation testing when whole-chromosome isodisomy is detected. |
format | Online Article Text |
id | pubmed-4802915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48029152016-03-23 Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features Aypar, Umut Hoppman, Nicole L. Thorland, Erik C. Dawson, D. Brian Mol Cytogenet Research BACKGROUND: Loss of expression of imprinted genes in the 15q11.2-q13 region is known to cause either Prader-Willi syndrome (PWS) or Angelman syndrome (AS), depending on the parent of origin. In some patients (1 % in PWS and 2–4 % in AS), the disease is due to aberrant imprinting or gene silencing, or both. RESULTS: We report here a 4-year-old boy on whom a chromosomal microarray (CMA) was performed due to mild hand tremors, mild developmental delays, and clumsiness. CMA revealed absence of heterozygosity (AOH) spanning the entire chromosome 15, suggesting uniparental isodisomy 15. The patient had no definitive phenotypic features of PWS or AS. Methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) was performed to determine the parent of origin of the uniparental disomy (UPD) by examining methylation status at maternally imprinted sites. Interestingly, our patient had a mosaic methylation pattern. We identified nine additional previously tested patients with a similar mosaic methylation pattern. CMA was performed on these individuals retrospectively to test whether patients with mosaic methylation are more likely to have UPD of chromosome 15. Of the nine patients, only one had regions of AOH on chromosome 15; however, this patient had numerous regions of AOH on multiple chromosomes suggestive of consanguinity. CONCLUSION: The patients with mosaic methylation had milder or atypical features of AS, and the majority also had some features characteristic of PWS. We suggest that quantitative methylation analysis be performed for cases of atypical PWS or AS. It is also important to follow up with methylation testing when whole-chromosome isodisomy is detected. BioMed Central 2016-03-22 /pmc/articles/PMC4802915/ /pubmed/27006693 http://dx.doi.org/10.1186/s13039-016-0233-0 Text en © Aypar et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Aypar, Umut Hoppman, Nicole L. Thorland, Erik C. Dawson, D. Brian Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features |
title | Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features |
title_full | Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features |
title_fullStr | Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features |
title_full_unstemmed | Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features |
title_short | Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features |
title_sort | patients with mosaic methylation patterns of the prader-willi/angelman syndrome critical region exhibit as-like phenotypes with some pws features |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802915/ https://www.ncbi.nlm.nih.gov/pubmed/27006693 http://dx.doi.org/10.1186/s13039-016-0233-0 |
work_keys_str_mv | AT ayparumut patientswithmosaicmethylationpatternsofthepraderwilliangelmansyndromecriticalregionexhibitaslikephenotypeswithsomepwsfeatures AT hoppmannicolel patientswithmosaicmethylationpatternsofthepraderwilliangelmansyndromecriticalregionexhibitaslikephenotypeswithsomepwsfeatures AT thorlanderikc patientswithmosaicmethylationpatternsofthepraderwilliangelmansyndromecriticalregionexhibitaslikephenotypeswithsomepwsfeatures AT dawsondbrian patientswithmosaicmethylationpatternsofthepraderwilliangelmansyndromecriticalregionexhibitaslikephenotypeswithsomepwsfeatures |