Using long-read sequencing to detect and subtype a case with Temple syndrome
Temple syndrome is an imprinting disorder resulting from abnormal genomic or epigenomic aberrations of chromosome 14 including maternal uniparental disomy (matUPD), paternal deletion of 14q32, or aberrant methylation of the imprinting control regions at 14q32. Understanding the underlying molecular mechanism is essential to understanding the recurrence risk and physical effects. Currently, diagnosis requires the detection of aberrant methylation and copy number loss via methylation-sensitive assays such as methylation-specific multiplex ligation-dependent probe amplification, and short tandem repeat analysis to detect matUPD and the presence of epimutation. Therefore, a one-step approach that can detect aberrant methylation and underlying genetic mechanisms would be of high clinical value. Here we use nanopore sequencing to delineate the molecular diagnosis of a case with Temple syndrome. We demonstrate the application of nanopore sequencing to detect aberrant methylation and underlying genetic mechanisms simultaneously in this case, thus providing a proof of concept for a one-step approach for molecular diagnosis of this disorder.
Authors
- Sanaa Choufani
- Sarah Dada (ORCID: https://orcid.org/0000-0002-3445-2377)
- Danya A. Fox (ORCID: https://orcid.org/0000-0002-5838-3599)
- Emma Strong
- Rosanna Weksberg (ORCID: https://orcid.org/0000-0002-6501-4150)
- Daniel Gamu (ORCID: https://orcid.org/0000-0001-7311-8008)
- Duha Hejla
- Katherine Dixon (ORCID: https://orcid.org/0000-0002-7334-888X)
- Vahid Akbari (ORCID: https://orcid.org/0000-0001-8005-7776)
- William T. Gibson (ORCID: https://orcid.org/0000-0002-6552-402X)
- Kamilla Schlade‐Bartusiak (ORCID: https://orcid.org/0000-0003-3226-7423)
- Laura Stewart (ORCID: https://orcid.org/0000-0003-1078-9722)
- Cornelius F. Boerkoel (ORCID: https://orcid.org/0000-0003-3097-241X)
- Steven J.M. Jones (ORCID: https://orcid.org/0000-0003-3394-2208)
- Yaoqing Shen (ORCID: https://orcid.org/0000-0002-7978-0008)
Institutions
- University of British Columbia (CA)
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Canada's Michael Smith Genome Sciences Centre (CA)
- BC Children's Hospital (CA)
- B.C. Women's Hospital & Health Centre (CA)
Publication Details
- Journal
- Journal of Medical Genetics
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1136/jmg-2024-110262
- Primary Topic
- Genetic Syndromes and Imprinting
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- BC Children's Hospital
- Canada Research Chairs
- Canadian Institutes of Health Research
- BC Cancer Agency