ArticleAmerican journal of human genetics2005
PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome.
Article in American journal of human genetics, 2005. 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 69 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
69 citing papers in PubMed, 243 citations in OpenAlex.
- Birth-related characteristics, congenital malformation, maternal reproductive history and neuroblastoma: the ESCALE study (SFCE).International journal of cancer · 2008Trial
- Redefining PHOX2B-Related Neurodevelopmental Disorders as Circuitopathies: A New Paradigm in Autonomic Network Medicine.Neuroscience bulletin · 2026Review
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.Nature communications · 2026Article
- International Congenital Central Hypoventilation Syndrome (CCHS) Registry: Analysis of Patient-Reported Symptoms by PHOX2B Variant.Pediatric pulmonology · 2026Article
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.bioRxiv : the preprint server for biology · 2025Article
- TheFrontiers in physiology · 2025Article
- Literature mining discerns latent disease-gene relationships.Bioinformatics (Oxford, England) · 2024Article
- Multifocal Neuroblastoma and Central Hypoventilation in An Infant with GermlineDiagnostics (Basel, Switzerland) · 2022Article
- A Deeper Curse: A Hirschsprung Patient's Evaluation Unmasks a Rare Association with Congenital Central Hypoventilation Syndrome and Neuroblastoma.European journal of pediatric surgery reports · 2022Article
- Genetic study of a patient with congenital central hypoventilation syndrome in Iran: a case report.Molecular biology reports · 2021Article
- Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS).Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice.Journal of molecular cell biology · 2021Article
- Review
- Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature.Translational pediatrics · 2021Article
- Hirschsprung disease and other gastrointestinal motility disorders in patients with CCHS.European journal of pediatrics · 2021Article
- How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center.Frontiers in pediatrics · 2021Article
- Negative Association Between lncRNAPharmacogenomics and personalized medicine · 2020Article
- Up-regulation of RNA Binding Proteins Contributes to Folate Deficiency-Induced Neural Crest Cells Dysfunction.International journal of biological sciences · 2020Article
- Optogenetic analysis of respiratory neuronal networks in the ventral medulla of neonatal rats producing channelrhodopsin in Phox2b-positive cells.Pflugers Archiv : European journal of physiology · 2019Article
- Associations betweenBioscience reports · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedNiemann, Stephan [added]
Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Phox2b gene is necessary for autonomic nervous-system development. Phox2b-/- mice die in utero with absent autonomic nervous system circuits, since autonomic nervous system neurons either fail to form or degenerate. We first identified the Phox2b human ortholog, PHOX2B, as the gene underlying congenital central hypoventilation syndrome (CCHS, or Ondine curse), with an autosomal dominant mode of inheritance and de novo mutation at the first generation. We have subsequently shown that heterozygous mutations of PHOX2B may account for several combined or isolated disorders of autonomic nervous-system development--namely, tumors of the sympathetic nervous system (TSNS), such as neuroblastoma and late-onset central hypoventilation syndrome. Here, we report the clinical and molecular assessments of a cohort of 188 probands with CCHS, either isolated or associated with Hirschsprung disease and/or TSNS. The mutation-detection rate was 92.6% (174/188) in our series, and the most prevalent mutation was an in-frame duplication leading to an expansion of +5 to +13 alanines in the 20-alanine stretch at the carboxy terminal of the protein. Such findings suggest PHOX2B mutation screening as a simple and reliable tool for the diagnosis of CCHS, independent of the clinically variable phenotype. In addition, somatic mosaicism was detected in 4.5% of parents. Most interestingly, analysis of genotype-phenotype interactions strongly supports the contention that patients with CCHS who develop malignant TSNS will harbor either a missense or a frameshift heterozygous mutation of the PHOX2B gene. These data further highlight the link between congenital malformations and tumor predisposition when a master gene in development is mutated.
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.