ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Genomic mosaicism in the pathogenesis and inheritance of a Rett syndrome cohort.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Germline mosaicism in TCF20-associated neurodevelopmental disorders: a case study and literature review.Journal of human genetics · 2025Review
- MECP2 Variants in Males: More Common than Previously Appreciated.Pediatric neurology · 2024Article
- [Sperm Mosaic Variants and Their Influence on the Offspring].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- MECP2 germline mosaicism plays an important part in the inheritance of Rett syndrome: a study of MECP2 germline mosaicism in males.BMC medicine · 2023Article
- Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation.Nature communications · 2023Article
- Sperm mosaicism: implications for genomic diversity and disease.Trends in genetics : TIG · 2021Review
- Technological Improvements in the Genetic Diagnosis of Rett Syndrome Spectrum Disorders.International journal of molecular sciences · 2021Review
- Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives.International journal of molecular sciences · 2021Review
- Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease.Biomolecules · 2021Review
- Difficulties of Prenatal Genetic Counseling for a Subsequent Child in a Family With Multiple Genetic Variations.Frontiers in genetics · 2021Article
- Case Report: Prenatal Diagnosis for a Rett Syndrome Family Caused by a NovelFrontiers in pediatrics · 2021Article
- Clinical and genetic characteristics and prenatal diagnosis of patients presented GDD/ID with rare monogenic causes.Orphanet journal of rare diseases · 2020Article
- Sex differences in Mecp2-mutant Rett syndrome model mice and the impact of cellular mosaicism in phenotype development.Brain research · 2020Review
- MeCP2_e2 partially compensates for lack of MeCP2_e1: A male case of Rett syndrome.Molecular genetics & genomic medicine · 2020Article
- Complex Mosaicism of Two Distinct Mutations in a Female Patient WithFrontiers in genetics · 2020Article
- In Silico Study of Rett Syndrome Treatment-Related Genes,International journal of molecular sciences · 2019Article
- Rett and Rett-like syndrome: Expanding the genetic spectrum to KIF1A and GRIN1 gene.Molecular genetics & genomic medicine · 2019Article
- Review
- A case of congenital Rett variant in a Chinese patient caused by aAnnals of Saudi medicineArticle
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo determine the role of mosaicism in the pathogenesis and inheritance of Rett and Rett-like disorders.
methodsWe recruited 471 Rett and Rett-like patients. Panel-sequencing targeting MECP2, CDKL5, and FOXG1 was performed. Mosaicism was quantified in 147 patients by a Bayesian genotyper. Candidates were validated by amplicon sequencing and digital PCR. Germline mosaicism of 21 fathers with daughters carrying pathogenic MECP2 variants was further quantified.
resultsPathogenic variants of MECP2/CDKL5/FOXG1 were found in 324/471 (68.7%) patients. Somatic MECP2 mosaicism was confirmed in 5/471 (1.1%) patients, including 3/18 males (16.7%) and 2/453 females (0.4%). Three of the five patients with somatic MECP2 mosaicism had mosaicism at MECP2-Arg106. Germline MECP2 mosaicism was detected in 5/21 (23.8%) fathers.
conclusionThis is the first systematic screening of somatic and paternal germline MECP2 mosaicism at a cohort level. Our findings indicate that somatic MECP2 mosaicism contributes directly to the pathogenicity of Rett syndrome, especially in male patients. MECP2-Arg106 might be a mosaic hotspot. The high proportion of paternal germline MECP2 mosaicism indicates an underestimated mechanism underlying the paternal origin bias of MECP2 variants. Finally, this study provides an empirical foundation for future studies of genetic disorders caused by de novo variations of strong paternal origin.
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