Service de Biochimie-Génétique, APHP, Groupe Hospitalier Henri Mondor-Albert Chenevier, UF de Génétique, Créteil, 94010, France.
Hum Genet. 2011 Apr;129(4):387-96. doi: 10.1007/s00439-010-0933-1. Epub 2010 Dec 24.
Fetal bowel anomalies may reveal cystic fibrosis (CF) and the search for CF transmembrane conductance regulator (CFTR) gene mutations is part of the diagnostic investigations in such pregnancies, according to European recommendations. We report on our 18-year experience to document comprehensive CFTR genotypes and correlations with ultrasound patterns in a series of 694 cases of fetal bowel anomalies. CFTR gene analysis was performed in a multistep process, including search for frequent mutations in the parents and subsequent in-depth search for rare mutations, depending on the context. Ultrasound patterns were correlated with the genotypes. Cases were distinguished according to whether they had been referred directly to our laboratory or after an initial testing in another laboratory. A total of 30 CF fetuses and 8 cases compatible with CFTR-related disorders were identified. CFTR rearrangements were found in 5/30 CF fetuses. 21.2% of fetuses carrying a frequent mutation had a second rare mutation, indicative of CF. The frequency of CF among fetuses with no frequent mutation was 0.43%. Correlation with ultrasound patterns revealed a significant frequency of multiple bowel anomalies in CF fetuses. The results emphasize the need to search for rearrangements in the diagnosis strategy of fetal bowel anomalies. The diagnostic value of ultrasound patterns combining hyperechogenic bowel, loop dilatation and/or non-visualized gallbladder reveals a need to revise current strategies and to offer extensive CFTR gene testing when the triad is diagnosed, even when no frequent mutation is found in the first-step analysis.
根据欧洲的建议，胎儿肠道异常可能提示囊性纤维化（CF），在这种情况下，寻找 CF 跨膜电导调节因子（CFTR）基因突变是诊断性检查的一部分。我们报告了 18 年来的经验，以记录 694 例胎儿肠道异常系列中 CFTR 综合基因型与超声模式的相关性。CFTR 基因分析采用多步过程进行，包括在父母中寻找常见突变，并根据具体情况对罕见突变进行深入搜索。将超声模式与基因型相关联。根据它们是直接转至我们实验室还是在另一个实验室进行初步检测进行区分。共发现 30 例 CF 胎儿和 8 例符合 CFTR 相关疾病的病例。在 30 例 CF 胎儿中发现了 5 例 CFTR 重排。携带常见突变的胎儿中有 21.2%存在第二种罕见突变，提示 CF。无常见突变的胎儿中 CF 的频率为 0.43%。与超声模式的相关性显示 CF 胎儿中多发性肠异常的频率较高。结果强调了在胎儿肠道异常的诊断策略中需要搜索重排的必要性。超声模式联合肠回声增强、肠环扩张和/或胆囊未显影的诊断价值提示需要修订当前策略，并在诊断三联征时提供广泛的 CFTR 基因检测，即使在第一步分析中未发现常见突变。
