title: CHRNG genotype-phenotype correlations in the multiple pterygium syndromes.
abstract: BACKGROUND
  Germline mutations in the CHRNG gene that encodes the γ subunit of the embryonal acetylcholine receptor may cause the non-lethal Escobar variant (EVMPS) or the lethal form (LMPS) of multiple pterygium syndrome (MPS). In addition CHRNG mutations and mutations in other components of the embryonal acetylcholine receptor may present with fetal akinesia deformation sequence (FADS) without pterygia.
  
  
  METHODS
  In order to elucidate further the role of CHRNG mutations in MPS/FADS, this study evaluated the results of CHRNG mutation analysis in 100 families with a clinical diagnosis of MPS/FADS.
  
  
  RESULTS
  CHRNG mutations were identified in 11/41 (27%) of families with EVMPS and 5/59 (8%) with LMPS/FADS. Most patients with a detectable CHRNG mutation (21 of 24 (87.5%)) had pterygia but no CHRNG mutations were detected in the presence of central nervous system anomalies.
  
  
  CONCLUSIONS
  The mutation spectrum was similar in EVMPS and LMPS/FADS kindreds and EVMPS and LMPS phenotypes were observed in different families with the same CHRNG mutation. Despite this intrafamilial variability, it is estimated that there is a 95% chance that a subsequent sibling will have the same MPS phenotype (EVMPS or LMPS) as the proband (though concordance is less for more distant relatives). Based on these findings, a molecular genetic diagnostic pathway for the investigation of MPS/FADS is proposed.
authors.affiliation: Centre for Rare Diseases and Personalised Medicine and Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. julie.vogt@bwhct.nhs.uk
authors.forename: Julie
authors.initials: J
authors.lastname: Vogt
authors.forename: Neil V
authors.initials: NV
authors.lastname: Morgan
authors.forename: Pauline
authors.initials: P
authors.lastname: Rehal
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brueton
authors.forename: Kristin
authors.initials: K
authors.lastname: Becker
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Sue
authors.initials: S
authors.lastname: Holder
authors.forename: Lily
authors.initials: L
authors.lastname: Islam
authors.forename: Emma
authors.initials: E
authors.lastname: Kivuva
authors.forename: Sally Ann
authors.initials: SA
authors.lastname: Lynch
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.forename: Louise C
authors.initials: LC
authors.lastname: Wilson
authors.forename: Fiona
authors.initials: F
authors.lastname: MacDonald
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008305:Malignant Hyperthermia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality; D009154:Mutation; D011247:Pregnancy; D011625:Pterygium / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality; D011978:Receptors, Nicotinic / Q000235:genetics*; D012868:Skin Abnormalities; D016216:Ultrasonography, Prenatal
chemical_list: C539275:CHRNG protein, human; D011978:Receptors, Nicotinic