ArticleAmerican journal of human genetics2008
Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders.
Article in American journal of human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin.The Journal of clinical investigation · 2016Trial
- Clinical Variability and Genotype-Driven Outcomes in CHRND-Related Congenital Myasthenic Syndrome.European journal of neurology · 2026Article
- Arthrogryposis Multiplex Congenita: Comprehensive Review from a Neuromuscular Standpoint.Genes · 2026Review
- Non-pterygium Escobar syndrome from compound-heterozygous CHRNG variants: genotype-phenotype insights.Human genome variation · 2026Article
- Review of 40 genes causing congenital myasthenic syndromes.Journal of human genetics · 2025Review
- Alteration of actin cytoskeletal organisation in fetal akinesia deformation sequence.Scientific reports · 2024Article
- The role of Rapsyn in neuromuscular junction and congenital myasthenic syndrome.Biomolecules & biomedicine · 2023Review
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Case Report: Early diagnosis of lethal multiple pterygium syndrome with micrognathia: Two novel mutations in theFrontiers in genetics · 2023Article
- Case Report: Novel compound heterozygous variants inFrontiers in genetics · 2022Article
- Article
- Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy.Cells · 2021Review
- Fetal akinesia deformation sequence with pontocerebellar hypoplasia, and migration and gyration defects.Autopsy & case reports · 2021Article
- Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts.Scientific reports · 2020Article
- A novel de novo nonsense mutation in ZC4H2 causes Wieacker-Wolff Syndrome.Molecular genetics & genomic medicine · 2020Article
- Compound heterozygous mutation ofWorld journal of clinical cases · 2019Article
- Molecular autopsy by trio exome sequencing (ES) and postmortem examination in fetuses and neonates with prenatally identified structural anomalies.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Italian recommendations for diagnosis and management of congenital myasthenic syndromes.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Article
- Utilization of Whole Exome Sequencing in Lethal Form of Multiple Pterygium Syndrome: Identification of Mutations in Embryonal Subunit of Acetylcholine Receptor.International journal of molecular and cellular medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired fetal movement causes malformations, summarized as fetal akinesia deformation sequence (FADS), and is triggered by environmental and genetic factors. Acetylcholine receptor (AChR) components are suspects because mutations in the fetally expressed gamma subunit (CHRNG) of AChR were found in two FADS disorders, lethal multiple pterygium syndrome (LMPS) and Escobar syndrome. Other AChR subunits alpha1, beta1, and delta (CHRNA1, CHRNB1, CHRND) as well as receptor-associated protein of the synapse (RAPSN) previously revealed missense or compound nonsense-missense mutations in viable congenital myasthenic syndrome; lethality of homozygous null mutations was predicted but never shown. We provide the first report to our knowledge of homozygous nonsense mutations in CHRNA1 and CHRND and show that they were lethal, whereas novel recessive missense mutations in RAPSN caused a severe but not necessarily lethal phenotype. To elucidate disease-associated malformations such as frequent abortions, fetal edema, cystic hygroma, or cardiac defects, we studied Chrna1, Chrnb1, Chrnd, Chrng, and Rapsn in mouse embryos and found expression in skeletal muscles but also in early somite development. This indicates that early developmental defects might be due to somite expression in addition to solely muscle-specific effects. We conclude that complete or severe functional disruption of fetal AChR causes lethal multiple pterygium syndrome whereas milder alterations result in fetal hypokinesia with inborn contractures or a myasthenic syndrome later in life.
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.