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.
J Med Genet. 2012 Jan;49(1):21-6. doi: 10.1136/jmedgenet-2011-100378.
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.
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.
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.
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.
编码胚胎乙酰胆碱受体γ亚基的 CHRNG 基因突变可能导致非致死性 Escobar 变异型（EVMPS）或致死性多翼畸形综合征（LMPS）。此外，CHRNG 基因突变和胚胎乙酰胆碱受体的其他成分的突变可能与翼状胬肉无关，表现为胎儿运动不能畸形序列（FADS）。
为了进一步阐明 CHRNG 基因突变在 MPS/FADS 中的作用，本研究评估了 100 个具有 MPS/FADS 临床诊断的家族中 CHRNG 基因突变分析的结果。
在 41 个 EVMPS 家族中有 11 个（27%）和 59 个 LMPS/FADS 家族中有 5 个（8%）发现 CHRNG 突变。大多数可检测到 CHRNG 突变的患者（24 例中的 21 例[87.5%]）有翼状胬肉，但在中枢神经系统异常的情况下没有检测到 CHRNG 突变。
EVMPS 和 LMPS/FADS 家族的突变谱相似，EVMPS 和 LMPS 表型在具有相同 CHRNG 突变的不同家族中观察到。尽管存在这种家族内的变异性，但估计随后的兄弟姐妹有相同的 MPS 表型（EVMPS 或 LMPS）作为先证者的可能性为 95%（尽管对于更远的亲属，一致性较低）。基于这些发现，提出了一种用于调查 MPS/FADS 的分子遗传诊断途径。
