Gestational Trophoblastic Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK.
J Med Genet. 2012 Mar;49(3):206-11. doi: 10.1136/jmedgenet-2011-100602. Epub 2012 Feb 7.
NLRP7 (NALP7) has been identified as the major gene involved in the inherited predisposition to recurrent molar pregnancies, a rare recessive condition in which affected individuals have complete hydatidiform moles of diploid biparental origin (BiCHM). The role of NLRP7 in other types of molar pregnancy and reproductive wastage has not been conclusively demonstrated. The purpose of this study was to clarify this by identifying NLRP7 variation in two clinically well-defined groups of patients: women with recurrent BiCHM, and women with three or more recurrent complete hydatidiform moles of proven androgenetic origin (AnCHM).
Fluorescent microsatellite genotyping of molar tissue was used to establish a diagnosis of recurrent BiCHM (four novel cases) or recurrent AnCHM (nine women with multiple CHM). These two groups were subsequently screened for mutations in NLRP7 using DNA sequencing. Additional screening for non-pathological variants was performed in 21 previously published cases of recurrent BiCHM. Taqman genotyping was used to determine the frequency of novel NLRP7 variants in two control cohorts of Caucasian and Asian women with no adverse reproductive outcomes.
Of the four novel cases with recurrent BiCHM, two were homozygous for mutations in NLRP7 while one was a compound heterozygote for a nonsense mutation and a pathological variant. No NLRP7 mutations or pathological variants were identified in the fourth case. None of the women with AnCHM carried any mutations or pathological variants of NLRP7. A single case of AnCHM was found to be heterozygous for a novel variant (R413Q).
NLRP7 mutations do not represent a major cause of AnCHM.
NLRP7（NALP7）已被确定为复发性葡萄胎遗传易感性的主要基因，这是一种罕见的隐性疾病，受影响个体具有完全的二倍体双亲来源的葡萄胎（BiCHM）。NLRP7 在其他类型的葡萄胎和生殖损耗中的作用尚未得到明确证实。本研究的目的是通过鉴定两种临床明确的患者群体中的 NLRP7 变异来阐明这一点：复发性 BiCHM 的女性，以及经证实为雄激素起源的三倍或更多复发性完全葡萄胎（AnCHM）的女性。
使用荧光微卫星基因分型对葡萄胎组织进行诊断，以确定复发性 BiCHM（四个新病例）或复发性 AnCHM（九名患有多发性 CHM 的女性）的诊断。随后使用 DNA 测序对这两组 NLRP7 进行突变筛查。在 21 例先前发表的复发性 BiCHM 病例中进行了非病理性变异的额外筛查。Taqman 基因分型用于确定两个高加索和亚洲女性对照组中 NLRP7 新型变体的频率，这些女性没有不良的生殖结局。
在四名复发性 BiCHM 的新病例中，两名是 NLRP7 突变的纯合子，一名是无义突变和病理性变异的复合杂合子。第四个病例未发现 NLRP7 突变或病理性变异。AnCHM 中的女性均未携带 NLRP7 的任何突变或病理性变异。在一个 AnCHM 病例中发现存在新型变体（R413Q）的杂合子。
NLRP7 突变不是 AnCHM 的主要原因。
