ArticleClinical genetics2012
Evidence for disease penetrance relating to CNV size: Pelizaeus-Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22.
Article in Clinical genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Complex genomic rearrangements: an underestimated cause of rare diseases.Trends in genetics : TIG · 2022Review
- CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.Cell genomics · 2022Article
- Contribution of Congenital Heart Disorders Associated With Copy Number Variants in Mediating Risk for Brain Developmental Disorders: Evidence From 20-Year Retrospective Cohort Study.Frontiers in cardiovascular medicine · 2021Article
- Cytogenetically visible inversions are formed by multiple molecular mechanisms.Human mutation · 2020Article
- A male infant with Xq22.2q22.3 duplication containing PLP1 and MID2.Molecular genetics & genomic medicine · 2020Article
- Xq22 deletions and correlation with distinct neurological disease traits in females: Further evidence for a contiguous gene syndrome.Human mutation · 2020Article
- Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants.Genome medicine · 2019Article
- From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability.Genome medicine · 2019Article
- Elucidation of the pathogenic mechanism and potential treatment strategy for a female patient with spastic paraplegia derived from a single-nucleotide deletion in PLP1.Journal of human genetics · 2019Article
- [Application of single nucleotide polymorphism microarray in clinical diagnosis of intellectual disability or retardation].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2019Article
- Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.PloS one · 2018Article
- Article
- Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease.European journal of human genetics : EJHG · 2017Article
- Efficient CNV breakpoint analysis reveals unexpected structural complexity and correlation of dosage-sensitive genes with clinical severity in genomic disorders.Human molecular genetics · 2017Article
- Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease.BMC medical genetics · 2015Article
- Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3.Human molecular genetics · 2015Article
- PacBio-LITS: a large-insert targeted sequencing method for characterization of human disease-associated chromosomal structural variations.BMC genomics · 2015Article
- Unusual presentation of pelizaeus-merzbacher disease: female patient with deletion of the proteolipid protein 1 gene.Case reports in genetics · 2015Article
- Replicative mechanisms for CNV formation are error prone.Nature genetics · 2013Article
- Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease.Human genetics · 2013Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The potential causes for the incomplete penetrance of Pelizaeus-Merzbacher disease (PMD) in female carriers of PLP1 mutations are not well understood. We present a family with a boy having PMD in association with PLP1 duplication and three females who are apparent manifesting carriers. Custom high-resolution oligonucleotide array comparative genomic hybridization (aCGH) and breakpoint junction sequencing were performed and revealed a familial complex duplication consisting of a small duplicated genomic interval (∼56 kb) and a large segmental duplication (∼11 Mb) that resulted in a PLP1 copy number variation gain. Breakpoint junction analysis implicates a replication-based mechanism underlying the rearrangement formation. X-inactivation studies (XCI) showed a random to moderate advantageous skewing pattern in peripheral blood cells but a moderate to extremely skewed (≥90%) pattern in buccal cells. In conclusion, our data show that complex duplications involving PLP1 are not uncommon, can be detected at the level of genome resolution afforded by clinical aCGH and duplication and inversion can be produced in the same event. Furthermore, the observation of three manifesting carriers with a large genomic rearrangement supports the contention that duplication size along with genomic content can be an important factor for penetrance of the PMD phenotype in females.
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