A Streamlined Approach to Prader-Willi and Angelman Syndrome Molecular Diagnostics
| Autor: | Joanna Liu, Mirandy Teguh, Harry Gao, Samuel P. Strom, Merlin G. Butler, Hai-Yun Yen, William A Scaringe, Waheeda A. Hossain, Mickey Li, Melina Grigorian, Joseph Fierro |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Prader–Willi syndrome point mutations Rett syndrome streamlined molecular diagnostics 030105 genetics & heredity Uniparental Heterodisomy QH426-470 03 medical and health sciences Angelman syndrome Genetics Medicine Copy-number variation Multiplex ligation-dependent probe amplification whole-exome sequencing Genetics (clinical) Exome sequencing Original Research methylation status business.industry Molecular diagnostics medicine.disease 030104 developmental biology Uniparental Isodisomy Molecular Medicine business copy number variants |
| Zdroj: | Frontiers in Genetics Frontiers in Genetics, Vol 12 (2021) |
| ISSN: | 1664-8021 |
| Popis: | Establishing or ruling out a molecular diagnosis of Prader–Willi or Angelman syndrome (PWS/AS) presents unique challenges due to the variety of different genetic alterations that can lead to these conditions. Point mutations, copy number changes, uniparental isodisomy (i-UPD) 15 of two subclasses (segmental or total isodisomy), uniparental heterodisomy (h-UPD), and defects in the chromosome 15 imprinting center can all cause PWS/AS. Here, we outline a combined approach using whole-exome sequencing (WES) and DNA methylation data with methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) to establish both the disease diagnosis and the mechanism of disease with high sensitivity using current standard of care technology and improved efficiency compared to serial methods. The authors encourage the use of this approach in the clinical setting to confirm and establish the diagnosis and genetic defect which may account for the secondary genetic conditions that may be seen in those with isodisomy 15, impacting surveillance and counseling with more accurate recurrence risks. Other similarly affected individuals due to other gene disorders or cytogenetic anomalies such as Rett syndrome or microdeletions would also be identified with this streamlined approach. |
| Databáze: | OpenAIRE |
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