Cholinergic Receptor, Nicotinic, Gamma Polypeptide (CHRNG; MIM#100730) is the gamma subunit of the Acetylcholine receptor (AChR). CHRNG is the variable subunit of AChR, which is present in humans before 33 weeks of gestational age and replaced by the 𝜀 subunit (CHRNE; MIM#100725) in late fetal and perinatal period. Fetal AChR is critical for establishing muscle-axon interface and neuromuscular junctions as well as prenatal neuromuscular signal transduction. Biallelic pathogenic variants in CHRNG are associated with CHRNG-associated hypo-akinesia disorder of prenatal onset (MONDO:0100158) with autosomal recessive inheritance pattern. Clinical phenotypes are variable include prenatal akinesia and associated resulting phenotypes, pterygium, poly- or oligohydramnios, intrauterine growth restriction, cystic hygroma, hydrops, reduced fetal movements, muscle weakness, congenital contractures, and fetal demise or stillbirth. The molecular etiology of CHRNG-associated disease was first reported by Hoffmann (2006; PMID:16826520) and Morgan (2006; PMID:16826531), and since has been reported in many additional male and female probands and found to segregate with disease in families and genetic evidence was scored at the maximum of 12 points [PMIDs:16826520, 16826531, 30868735, 34440395]. Functional evidence including expression studies [PMID:18252226, 16826520] and a mouse model recapitulating the observed human phenotype [PMID:12101101] were scored for an additional 3.0 points. Given this and its replication in the literature over time, the association of CHRNG with CHRNG-associated hypo-akinesia disorder of prenatal onset is curated as Definitive by the Prenatal Gene Curation Expert Panel.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.