Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):211-5. doi: 10.1016/j.ejogrb.2012.06.017. Epub 2012 Jul 4.
Hydatidiform mole is an aberrant pregnancy with hyperproliferative vesicular trophoblast and defective fetal development. In 2006, mutations in NLRP7 were found to be responsible for recurrent hydatidiform moles (RHM), but genetic heterogeneity has been demonstrated and mutations of C6orf221 were later reported in several families. Here we report a new Egyptian family in which two sisters had eleven and four molar pregnancies, respectively. The objective was to present the results of the mutation analysis of NLRP7 and C6orf221 genes in Egyptian women with RHM.
Three women from two unrelated Egyptian families; two sisters and a previously described sporadic case, all presenting with RHM, were enrolled. The cases were subjected to detailed history taking, karyotyping and screening for mutations in NLRP7 and C6orf221.
Two NLRP7 mutations have been detected, one in each family. In the first family, sequencing identified a homozygous 2 bp deletion in the seventh coding exon of NLRP7, while a homozygous G-to-A substitution in the third coding exon of NLRP7 was detected in the second family. Both of them result in a truncated protein. The two mutations have not been previously described in the literature. No mutations in C6orf221 were found in any of the samples.
The detection of an NLRP7 mutation in both the familial and the apparently isolated case of RHM provides further evidence for the previously established role of NLRP7 mutations in the pathophysiology of RHM and increases the diversity of mutations described in the Egyptian population. Our results also expand further the spectrum of reproductive wastage associated with NLRP7 mutations to patients with recurrent spontaneous abortion.
葡萄胎是一种异常妊娠，其特征为增生的葡萄状滋养层和胎儿发育缺陷。2006 年，发现 NLRP7 的突变与复发性葡萄胎（RHM）有关，但已证实存在遗传异质性，随后在多个家族中报道了 C6orf221 的突变。本研究报道了一个新的埃及家系，其中两名姐妹分别发生了 11 次和 4 次葡萄胎。目的是报告埃及 RHM 妇女 NLRP7 和 C6orf221 基因突变分析的结果。
纳入了两个不相关的埃及家庭的 3 名妇女；两名姐妹和之前描述的散发性病例，均患有 RHM。对这些病例进行了详细的病史询问、核型分析和 NLRP7 和 C6orf221 基因突变筛查。
在两个家庭中都发现了 2 个 NLRP7 突变，一个家庭中有一个，另一个家庭中有一个。在第一个家庭中，测序发现 NLRP7 第 7 个编码外显子的 2 个碱基缺失，而在第二个家庭中检测到 NLRP7 的第 3 个编码外显子的 G 到 A 取代。这两种突变都会导致截短的蛋白。这两种突变以前都没有在文献中描述过。在任何样本中都没有发现 C6orf221 的突变。
在家族性和明显孤立的 RHM 病例中均检测到 NLRP7 突变，进一步证明 NLRP7 突变在 RHM 的病理生理学中的作用，并增加了在埃及人群中描述的突变多样性。我们的结果还进一步扩展了与 NLRP7 突变相关的生殖不良的范围，包括复发性自然流产患者。
