ArticlePLoS genetics2011
CtIP Mutations Cause Seckel and Jawad Syndromes.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- Meta-analysis of DNA double-strand break response kinetics.Nucleic acids research · 2017Pooled it
- Evaluation of genetic risk loci for intracranial aneurysms in sporadic arteriovenous malformations of the brain.Journal of neurology, neurosurgery, and psychiatry · 2015Pooled it
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
- ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome.Nature cell biology · 2025Article
- Clinical Challenges in Diagnosing Primordial Dwarfism: Insights from a MOPD II Case Study.Medicina (Kaunas, Lithuania) · 2024Article
- DNA binding and bridging by human CtIP in the healthy and diseased states.Nucleic acids research · 2024Article
- Centriolar subdistal appendages promote double-strand break repair through homologous recombination.EMBO reports · 2023Article
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
- Recurrence mutation in RBBP8 gene causing non-syndromic autosomal recessive primary microcephaly; geometric simulation approach for insight into predicted computational models.Journal of human genetics · 2023Article
- Rothmund-Thomson syndrome, a disorder far from solved.Frontiers in aging · 2023Review
- A Genetic Approach in the Evaluation of Short Stature.The Eurasian journal of medicine · 2022Article
- Time is of the essence: the molecular mechanisms of primary microcephaly.Genes & development · 2021Review
- High proliferation and delamination during skin epidermal stratification.Nature communications · 2021Article
- Mechanistic Modelling of Slow and Fast NHEJ DNA Repair Pathways Following Radiation for G0/G1 Normal Tissue Cells.Cancers · 2021Article
- A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- Meiotic Recombination Defects and Premature Ovarian Insufficiency.Frontiers in cell and developmental biology · 2021Review
- Complex Phenotypes: Mechanisms Underlying Variation in Human Stature.Current osteoporosis reports · 2019Review
- CtIP is essential for telomere replication.Nucleic acids research · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and a unique head profile. Genetically, it constitutes a heterogeneous condition, with several loci mapped (SCKL1-5) but only three disease genes identified: the ATR, CENPJ, and CEP152 genes that control cellular responses to DNA damage. We previously mapped a Seckel syndrome locus to chromosome 18p11.31-q11.2 (SCKL2). Here, we report two mutations in the CtIP (RBBP8) gene within this locus that result in expression of C-terminally truncated forms of CtIP. We propose that these mutations are the molecular cause of the disease observed in the previously described SCKL2 family and in an additional unrelated family diagnosed with a similar form of congenital microcephaly termed Jawad syndrome. While an exonic frameshift mutation was found in the Jawad family, the SCKL2 family carries a splicing mutation that yields a dominant-negative form of CtIP. Further characterization of cell lines derived from the SCKL2 family revealed defective DNA damage induced formation of single-stranded DNA, a critical co-factor for ATR activation. Accordingly, SCKL2 cells present a lowered apoptopic threshold and hypersensitivity to DNA damage. Notably, over-expression of a comparable truncated CtIP variant in non-Seckel cells recapitulates SCKL2 cellular phenotypes in a dose-dependent manner. This work thus identifies CtIP as a disease gene for Seckel and Jawad syndromes and defines a new type of genetic disease mechanism in which a dominant negative mutation yields a recessively inherited disorder.
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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.