title: Rare cases of congenital arthrogryposis multiplex caused by novel recurrent CHRNG mutations.
abstract: Multiple pterygium syndrome (MPS) is an autosomal recessively inherited condition that becomes evident before birth, with pterygium at multiple joints and akinesia. There are two forms of this syndrome that are differentiated by clinical severity: the milder form, Escobar type (OMIM#265000), and the more severe form, lethal type (OMIM#253290). Mutations in CHRNG, which encode the acetylcholine receptor gamma subunit, cause most cases of MPS. Here, we present three patients from two unrelated families showing multiple joint contractures in both the upper and lower limbs. High-arched palates with malocclusion, short neck and micrognathia were observed in all patients. Peripheral blood karyotypes were normal. Whole-exome sequencing analysis of the patients' genomes led to the discovery of identical missense (p.Pro143Arg) and frameshift deletion variants (p.Pro251fs*45) on CHRNG. These were rare cases of congenital arthrogryposis multiplex related to novel recessive CHRNG variants in two Korean kindred without apparent relatedness.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Seo
authors.affiliation: Department of Orthopedic Surgery, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Choi
authors.affiliation: Department of Rehabilitative Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Pusan, Korea.
authors.forename: Je Sang
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Yoo
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Nayoung K D
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Jung Min
authors.identifier: 0000000204077828
authors.initials: JM
authors.lastname: Ko
authors.affiliation: Department of Rehabilitative Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Pusan, Korea.
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Shin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001176:Arthrogryposis / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: C539275:CHRNG protein, human; D011978:Receptors, Nicotinic