CHRNG genotype–phenotype correlations in the multiple pterygium syndromes
Journal of medical genetics, 2012•jmg.bmj.com
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 …
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 …
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.
Discussion
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.
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