ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS).
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Transitional care and clinical management of adolescents, young adults, and suspected new adult patients with congenital central hypoventilation syndrome.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023Pooled it
- 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
- Regulation of PHOX2B gene expression by the long non-coding natural antisense RNA PHOX2B-AS1.The FEBS journal · 2026Article
- PHOX2B defects alter protein folding, cell-cycle, and mitochondrial pathways in an in vitro model of CCHS.Molecular medicine (Cambridge, Mass.) · 2026Article
- International Congenital Central Hypoventilation Syndrome (CCHS) Registry: Analysis of Patient-Reported Symptoms by PHOX2B Variant.Pediatric pulmonology · 2026Article
- Review
- PHOX2B deletion in congenital central hypoventilation syndrome: is this sufficient for pathogenesis?Journal of human genetics · 2026Article
- Article
- Recognition of a Critical Functional Domain and ImprovedHuman mutation · 2026Article
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.bioRxiv : the preprint server for biology · 2025Article
- Images: Atypical resolution of sleep-related hypoventilation in congenital central hypoventilation syndrome.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Article
- Neuroanatomical and neurochemical organization of brainstem and forebrain circuits involved in breathing regulation.Journal of neurophysiology · 2025Review
- TheFrontiers in physiology · 2025Article
- Genetic identification of medullary neurons underlying congenital hypoventilation.Science advances · 2024Article
- Computer-aided diagnostic screen for Congenital Central Hypoventilation Syndrome with facial phenotype.Pediatric research · 2024Article
- Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?Respiratory physiology & neurobiology · 2024Article
- Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature.Molecular genetics & genomic medicine · 2023Review
- Congenital Central Hypoventilation Syndrome in Israel-Novel Findings from a New National Center.Journal of clinical medicine · 2023Article
- Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCCHS is an extremely rare congenital disorder requiring artificial ventilation as life support. Typically caused by heterozygous polyalanine repeat expansion mutations (PARMs) in the PHOX2B gene, identification of a relationship between PARM length and phenotype severity has enabled anticipatory management. However, for patients with non-PARMs in PHOX2B (NPARMs, ~10% of CCHS patients), a genotype-phenotype correlation has not been established. This comprehensive report of PHOX2B NPARMs and associated phenotypes, aims at elucidating potential genotype-phenotype correlations that will guide anticipatory management.
methodsAn international collaboration (clinical, commercial, and research laboratories) was established to collect/share information on novel and previously published PHOX2B NPARM cases. Variants were categorized by type and gene location. Categorical data were analyzed with chi-square and Fisher's exact test; further pairwise comparisons were made on significant results.
resultsThree hundred two individuals with PHOX2B NPARMs were identified, including 139 previously unreported cases. Findings demonstrate significant associations between key phenotypic manifestations of CCHS and variant type, location, and predicted effect on protein function.
conclusionThis study presents the largest cohort of PHOX2B NPARMs and associated phenotype data to date, enabling genotype-phenotype studies that will advance personalized, anticipatory management and help elucidate pathological mechanisms. Further characterization of PHOX2B NPARMs demands longitudinal clinical follow-up through international registries.
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