ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2013
Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- A NOTCH2 pathogenic variant and HES1 regulate osteoclastogenesis in induced pluripotent stem cells.Bone · 2025Article
- Article
- Article
- Hajdu-Cheney syndrome with atypical cardiovascular abnormalities.American journal of medical genetics. Part A · 2023Article
- Hajdu Cheney syndrome; A novel NOTCH2 mutation in a Syrian child, and treatment with zolidronic acid: A case report and a literature review of treatments.Annals of medicine and surgery (2012) · 2021Article
- Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature.Orphanet journal of rare diseases · 2021Article
- Hajdu Cheney Syndrome due to NOTCH2 defect - First case report from Pakistan and review of literature.Annals of medicine and surgery (2012) · 2021Article
- Review
- Antisense oligonucleotides targetingThe Journal of biological chemistry · 2020Article
- Distinct severity of phenotype in Hajdu-Cheney syndrome: a case report and literature review.BMC musculoskeletal disorders · 2020Review
- The Hajdu Cheney mutation sensitizes mice to the osteolytic actions of tumor necrosis factor α.The Journal of biological chemistry · 2019Article
- Notch in skeletal physiology and disease.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2018Review
- Article
- Induction of the Hajdu-Cheney Syndrome Mutation in CD19 B Cells in Mice Alters B-Cell Allocation but Not Skeletal Homeostasis.The American journal of pathology · 2018Article
- Clinical and experimental aspects of notch receptor signaling: Hajdu-Cheney syndrome and related disorders.Metabolism: clinical and experimental · 2018Review
- The Hajdu Cheney Mutation Is a Determinant of B-Cell Allocation of the Splenic Marginal Zone.The American journal of pathology · 2018Article
- Bone Structural Characteristics and Response to Bisphosphonate Treatment in Children With Hajdu-Cheney Syndrome.The Journal of clinical endocrinology and metabolism · 2017Article
- Sustained Notch2 signaling in osteoblasts, but not in osteoclasts, is linked to osteopenia in a mouse model of Hajdu-Cheney syndrome.The Journal of biological chemistry · 2017Article
- An Antibody to Notch2 Reverses the Osteopenic Phenotype of Hajdu-Cheney Mutant Male Mice.Endocrinology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledThe Hajdu-Cheney syndrome is a very rare disease that affects several organ system, leading to severe osteoporosis and other abnormalities. We describe clinical and genetic findings of nine patients with this disease.
introductionThe Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts, and other abnormalities. Recently, heterozygous mutations in NOTCH2 were identified as the cause of HCS.
methodsNine patients with typical presentations of HCS took part in this study: five affected patients from two small families and four sporadic cases. Peripheral blood DNA was obtained and exome sequencing performed in one affected individual per family and in all four sporadic cases. Sanger sequencing confirmed mutations in all patients.
resultsOne of the identified mutations was introduced in a plasmid encoding NOTCH2. Wild-type and mutant NOTCH2 were transiently expressed in HEK293 cells to assess intracellular localization after ligand activation. Deleterious heterozygous mutations in the last NOTCH2 exon were identified in all patients; five of the six mutations were novel.
conclusionConsistent with previous reports, all mutations are predicted to result in a loss of the proline/glutamic acid/serine/threonine sequence, which harbors signals for degradation, therefore suggesting activating mutations. One of the six mutations furthermore predicted disruption of the second nuclear localization signal of NOTCH2, but the mutant revealed normal nuclear localization after transfection, which is consistent with the proposed gain-of-function mechanism as the cause of this autosomal dominant disease. Our findings confirm that heterozygous NOTCH2 mutations are the cause of HCS and expand the mutational spectrum of this disorder.
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.