Absence of KHDC3L mutations in Chinese patients with recurrent and sporadic hydatidiform moles Wei Zhao a , ALaNuEr Muhetaer b , TengFei Luo b , Wei Zhou a , Cheng Qi b , XiaoDuan Chen b , XiaoFei Zhang b , ZhiFen Zhang c , Christine Dery d,e , Rima Slim d,e, *, JianHua Qian a,b, * a First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China; b Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China; c Affiliated Hangzhou Hospital of Nan Jing Medical University, Hangzhou, China; d Department of Human Genetics, McGill University Health Centre Research Institute, Montreal, Canada; e Department of Obstetrics and Gynecology, McGill University Health Centre Research Institute, Montreal, Canada To date, two maternal-effect genes have been shown to play causal roles in recurrent hydatidi- form moles (RHMs). NLRP7, a major gene for this condition, codes for a nucleotide-binding olig- omerization domain-like receptor and is mutated in 48 to 60% of patients with RHMs. KHDC3L is a recently identified gene that is mutated in 14% of NLRP7-negative patients. We screened KHDC3L for mutations in a total of 101 Chinese patients, 15 with at least two hydatidiform moles, 16 with at least two reproductive losses including one hydatidiform mole, and 70 with one hyda- tidiform mole and no other form of reproductive loss, but did not find any mutation. Our data favor the causal role of KHDC3L in a minority of RHM cases, demonstrate its noninvolvement in other forms of reproductive loss, and indicate the presence of other unidentified genes that cause or increase patients’ susceptibility to RHMs in the Chinese population. Keywords KHDC3L, hydatidiform moles, recurrent, sporadic, reproductive loss, Chinese population ª 2013 Elsevier Inc. All rights reserved. A hydatidiform mole (HM) is a human pregnancy with no embryo, abnormal trophoblastic proliferation, and cystic degeneration of chorionic villi. The common form of this con- dition occurs once in every 1,000 to 1,500 pregnancies in Western countries but at higher frequencies in several un- derdeveloped and developing countries (1). In China, the reported incidence of HMs varies from 1 to 8.83 in every 1,000 pregnancies, with the highest incidence occurring in the province of Zhejiang (2). Although the common form of this condition is sporadic, 1e6% of patients will have a se- cond mole, and about 10e20% will have a second nonmolar reproductive loss, most commonly as a spontaneous abortion. Because the frequency of spontaneous abortions in patients with a prior mole (10-20%) is higher than the frequency of recurrent spontaneous abortions reported in various pop- ulations, 2e5%, it is believed that patients with one mole have a genetic susceptibility to reproductive loss (3). Molar preg- nancies are usually benign but may degenerate into invasive moles or choriocarcinomas. The frequency of choriocarci- nomas is one in every 40,000e70,000 pregnancies in North America but is much higher in China where it reaches one in every 15,681 pregnancies (2). Familial occurrence of recurrent HMs (RHMs) is rare, and the analyses of such cases have led to the identification of a major autosomal recessive gene, NLRP7, responsible for this condition (4). Mutations in NLRP7 have been reported in pa- tients with RHMs from several populations (5e16) and were found in 88% and 66% of analyzed familial and singleton cases, respectively. These various mutations are listed on Internet Fevers; http://fmf.igh.cnrs.fr/ISSAID/infevers (17). In Chinese patients, mutations in NLRP7 were found in 48% of cases with at least two HMs (8). In addition, rare non- synonymous variants (NSVs), which are present in the gen- eral population, were found at higher frequencies in patients with recurrent reproductive loss (18). These rare variants and mutations are usually present in a heterozygous state, only on one allele, and are believed to increase the risk of patients for sporadic moles and reproductive loss (7,19). Received March 18, 2013; received in revised form September 2, 2013; accepted September 23, 2013. * Corresponding authors. E-mail addresses: rima.slim@muhc.mcgill.ca, qianjh987@ hotmail.com 2210-7762/$ - see front matter ª 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cancergen.2013.09.003 Cancer Genetics 206 (2013) 327e329