ArticleAmerican journal of medical genetics. Part A2020
Whole-genome sequencing reveals complex chromosome rearrangement disrupting NIPBL in infant with Cornelia de Lange syndrome.
Article in American journal of medical genetics. Part A, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Identification of De Novo Chromosomal Translocations Disrupting NIPBL in a Patient With Cornelia de Lange Syndrome by Full Genome Analysis.Molecular genetics & genomic medicine · 2025Article
- Structural and Mechanistic Diversity of Constitutional Chromoanagenesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Complex chromosomal rearrangements in female carriers experiencing recurrent pregnancy loss or poor obstetric history and literature review.Journal of assisted reproduction and genetics · 2025Review
- Article
- Resolving complex duplication variants in autism spectrum disorder using long-read genome sequencing.Genome research · 2024Article
- Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia.Nature communications · 2024Article
- Single variant, yet "double trouble": TSC and KBG syndrome because of a large de novo inversion.Life science alliance · 2024Article
- Long-read sequencing reveals chromothripsis in a molecularly unsolved case of Cornelia de Lange syndrome.Frontiers in genetics · 2024Article
- Organizational Aspects of the Implementation and Use of Whole Genome Sequencing and Whole Exome Sequencing in the Pediatric Population in Italy: Results of a Survey.Journal of personalized medicine · 2023Article
- Complex genomic rearrangements: an underestimated cause of rare diseases.Trends in genetics : TIG · 2022Review
- RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing.HGG advances · 2022Article
- Copy Number Variation Analysis of 5p Deletion Provides Accurate Prenatal Diagnosis and Reveals Candidate Pathogenic Genes.Frontiers in medicine · 2022Article
- Fine Breakpoint Mapping by Genome Sequencing Reveals the First Large X Inversion Disrupting theInternational journal of molecular sciences · 2021Article
- Clan genomics: From OMIM phenotypic traits to genes and biology.American journal of medical genetics. Part A · 2021Article
- Long-read genome sequencing for the molecular diagnosis of neurodevelopmental disorders.HGG advances · 2021Article
- Chromoanagenesis Event Underlies aFrontiers in genetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Clinical laboratory diagnostic evaluation of the genomes of children with suspected genetic disorders, including chromosomal microarray and exome sequencing, cannot detect copy number neutral genomic rearrangements such as inversions, balanced translocations, and complex chromosomal rearrangements (CCRs). We describe an infant with a clinical diagnosis of Cornelia de Lange syndrome (CdLS) in whom chromosome analysis revealed a de novo complex balanced translocation, 46,XY,t(5;7;6)(q11.2;q32;q13)dn. Subsequent molecular characterization by whole-genome sequencing (WGS) identified 23 breakpoints, delineating segments derived from four chromosomes (5;6;7;21) in ancestral or inverted orientation. One of the breakpoints disrupted a known CdLS gene, NIPBL. Further investigation revealed paternal origin of the CCR allele, clustering of the breakpoint junctions, and molecular repair signatures suggestive of a single catastrophic event. Notably, very short DNA segments (25 and 41 bp) were included in the reassembled chromosomes, lending additional support that the DNA repair machinery can detect and repair such segments. Interestingly, there was an independent paternally derived miniscule complex rearrangement, possibly predisposing to subsequent genomic instability. In conclusion, we report a CCR causing a monogenic Mendelian disorder, urging WGS analysis of similar unsolved cases with suspected Mendelian disorders. Breakpoint analysis allowed for identification of the underlying molecular diagnosis and implicated chromoanagenesis in CCR formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.