ArticleAmerican journal of medical genetics. Part A2017
Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome.
Article in American journal of medical genetics. Part A, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Article
- TheFrontiers in physiology · 2025Article
- [Two children with late-onset congenital central hypoventilation syndrome].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2023Article
- Case Report: A novelFrontiers in pediatrics · 2022Article
- 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
- Reduced PHOX2B stability causes axonal growth impairment in motor neurons with TARDBP mutations.Stem cell reports · 2021Article
- Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature.Translational pediatrics · 2021Article
- Article
- A respiratory/Hirschsprung phenotype in a three-generation family associated with a novel pathogenic PHOX2B splice donor mutation.Molecular genetics & genomic medicine · 2020Article
- A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon.Human molecular genetics · 2018Article
- Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of FOXP1.Scientific reports · 2018Article
- Atypical presentations associated with non-polyalanine repeat PHOX2B mutations.American journal of medical genetics. Part A · 2018Article
- Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.American journal of medical genetics. Part A · 2018Article
- Genotype-phenotype investigation of 35 patients from 11 unrelated families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.Molecular genetics & genomic medicine · 2018Article
- Loss of αB-crystallin function in zebrafish reveals critical roles in the development of the lens and stress resistance of the heart.The Journal of biological chemistry · 2018Article
- The genetics of congenital central hypoventilation syndrome: clinical implications.The application of clinical genetics · 2018Review
- Carbamazepine Improves Apneic Episodes in Congenital Central Hypoventilation Syndrome (CCHS) With a NovelJournal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2017Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Pathogenic variants in PHOX2B lead to congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by autonomic dysregulation and hypoventilation typically presenting in the neonatal period, although a milder late-onset (LO) presentation has been reported. More than 90% of cases are caused by polyalanine repeat mutations (PARMs) in the C-terminus of the protein; however non-polyalanine repeat mutations (NPARMs) have been reported. Most NPARMs are located in exon 3 of PHOX2B and result in a more severe clinical presentation including Hirschsprung disease (HSCR) and/or peripheral neuroblastic tumors (PNTs). A previously reported nonsense pathogenic variant in exon 1 of a patient with LO-CCHS and no HSCR or PNTs leads to translational reinitiation at a downstream AUG codon producing an N-terminally truncated protein. Here we report additional individuals with nonsense pathogenic variants in exon 1 of PHOX2B. In vitro analyses were used to determine if these and other reported nonsense variants in PHOX2B exon 1 produced N-terminally truncated proteins. We found that all tested nonsense variants in PHOX2B exon 1 produced a truncated protein of the same size. This truncated protein localized to the nucleus and transactivated a target promoter. These data suggest that nonsense pathogenic variants in the first exon of PHOX2B likely escape nonsense mediated decay (NMD) and produce N-terminally truncated proteins functionally distinct from those produced by the more common PARMs.
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