Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression
In aggregate, this combined analysis uncovers an interplay between MECP2 dosage, genomic rearrangement structure and phenotypic traits. Whereas the level of MECP2 is a key determinant of the phenotype, the DNA rearrangement structure can contribute to clinical severity and disease expression variability. Employing this type of analytical approach will advance our understanding of the impact of genomic rearrangements on genomic disorders and may help guide more targeted therapeutic approaches.
Authors
- James R. Lupski (ORCID: https://orcid.org/0000-0001-9907-9246)
- Marwan S. Shinawi (ORCID: https://orcid.org/0000-0003-1329-4100)
- Christopher M. Grochowski (ORCID: https://orcid.org/0000-0002-3884-7720)
- Zhandong Liu (ORCID: https://orcid.org/0000-0002-7608-0831)
- Daniel G. Glaze (ORCID: https://orcid.org/0000-0001-6846-6446)
- Cemal Karakas (ORCID: https://orcid.org/0000-0002-9516-2285)
- Melissa B. Ramocki
- Shin Nabatame (ORCID: https://orcid.org/0000-0001-8453-2028)
- Alexander J. Trostle (ORCID: https://orcid.org/0000-0001-5028-0184)
- Huda Y. Zoghbi (ORCID: https://orcid.org/0000-0002-0700-3349)
- Jesper Eisfeldt (ORCID: https://orcid.org/0000-0003-3716-4917)
- Jesse D. Bengtsson
- Wojciech Wiszniewski
- Davut Pehli̇van (ORCID: https://orcid.org/0000-0001-5788-0270)
- Kyle McKenzie
- Mira Gandhi
- KyungHee Park
- Holly K. Harris (ORCID: https://orcid.org/0000-0001-5512-755X)
- Fritz Joachim Sedlazeck (ORCID: https://orcid.org/0000-0001-6040-2691)
- Alberto S. Cornier (ORCID: https://orcid.org/0000-0003-4225-5397)
- Jawid M. Fatih (ORCID: https://orcid.org/0000-0002-3927-2711)
- Sameer S. Bajikar (ORCID: https://orcid.org/0000-0002-8868-881X)
- Michele G. Mehaffey
- Virginia Kimonis (ORCID: https://orcid.org/0000-0003-1567-4449)
- Maria Pettersson (ORCID: https://orcid.org/0000-0003-3120-1625)
- Richard A. Gibbs (ORCID: https://orcid.org/0000-0002-1356-5698)
- Lynn Liu
- Angela Maria Vianna‐Morgante (ORCID: https://orcid.org/0000-0003-1473-9669)
- Timo Roser (ORCID: https://orcid.org/0000-0002-9807-6956)
- Ahmed Abdelmoity (ORCID: https://orcid.org/0000-0002-0625-5464)
- Shalini N. Jhangiani (ORCID: https://orcid.org/0000-0002-6674-0074)
- Kazuhiro Muramatsu (ORCID: https://orcid.org/0000-0001-9256-5591)
- Anna Lindstrand (ORCID: https://orcid.org/0000-0003-0806-5602)
- Claudia M.B. Carvalho (ORCID: https://orcid.org/0000-0002-2090-298X)
- Haowei Du (ORCID: https://orcid.org/0000-0001-9052-1587)
- Bernhard Suter (ORCID: https://orcid.org/0000-0002-0127-7322)
- Tadahiro Mitani
- Angad Jolly (ORCID: https://orcid.org/0000-0002-5663-1157)
- Ming Yin Lun
- James Paul Hwang
- Donna M. Muzny
- Sukru Aras
- Ellen Wilkey
Institutions
- University of North Carolina at Chapel Hill (US)
- Pacific Northwest Diabetes Research Institute (US)
- Children's Mercy Hospital (US)
- Howard Hughes Medical Institute (US)
- University of Louisville (US)
- Jichi Medical University (JP)
- University of Alberta (CA)
- Oregon Health & Science University (US)
- Baylor College of Medicine (US)
- University of California, Irvine (US)
- Washington University in St. Louis (US)
- Karolinska Institutet (SE)
- San Juan City Hospital (PR)
- Neurological Research Institute (US)
- Texas Children's Hospital (US)
- Brazilian Biosciences National Laboratory (BR)
- Baylor Genetics (US)
- University of Greenwich (GB)
- Ludwig-Maximilians-Universität München (DE)
- Center for Autism and Related Disorders (US)
- The University of Osaka (JP)
Publication Details
- Journal
- Genome Medicine
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1186/s13073-024-01411-7
- Citations
- 15
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 8.25
Funders
- International Rett Syndrome Foundation
- Johns Hopkins University
- Baylor-Hopkins Center for Mendelian Genomics
- National Institutes of Health
- Intellectual and Developmental Disabilities Research Center
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke