1.Family pedigree analysis in family member with history of hydatidiform mole and the NLRP7 gene expression
Yong LI ; Qi CHENG ; Jianhua QIAN ; Wei ZHOU ; Xing XIE ; Slim RIMA
Chinese Journal of Obstetrics and Gynecology 2011;46(8):600-604
Objective To evaluate the NLRP7 gene mutations and variants and their expression of genetic approach in hydatidiform mole patients with family history.Methods Six cases of mole patients with family members of mole history and 60 healthy women, taking blood, extracting DNA, the genetic mutation on NLRP7 screening and analysis, looking for mutations and corresponding amino acids, proteins control gene mutation found NLRP7 area.Results In 6 mole patients with family history:three patients were with sister's history of mole, and 2 of them familial recurrent hydatidiform mole(from family MoCh76 and family Ch77), there are 2 loci NLRP7 gene mutation.Screening patients from family MoCh76 for mutations in NLRP7 revealed in exon 3 and exon 5, amino acids [295G > T] and [1970A > T], proteins [Glu99X] and [Asp657Val], in a heterozygous.Screening patients from family Ch77 for mutations in NLRP7 revealed in exon4 and exon 7, amino acids [1294C > T] and [2471 + 1G > A], proteins [Arg432X] and [Leu825X], in a heterozygous.Screening patients from family 105 for mutations in NLRP7 revealed no NLRP7 gene mutation.There were mother's history of mole in three patients, and they were not familial recurrent hydatidiform mole.Screening patients from family MoCh73 for mutations in NLRP7revealed in exon 4, amino acids [1137G > C], proteins [Lys379Asn], in a heterozygous.Screening patients from family 106 and family 110 for mutations in NLRP7 revealed no NLRP7 gene mutation.There were not found mutations and variations in 60 cases of ethnic matched control group.Conclusion NLRP7 mutations may be lead to familial recurrent hydatidiform mole.
2.Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during in vitro fertilization.
E Scott SILLS ; Alexandra J OBREGON-TITO ; Harry GAO ; Thomas K MCWILLIAMS ; Anthony T GORDON ; Catharine A ADAMS ; Rima SLIM
Clinical and Experimental Reproductive Medicine 2017;44(1):40-46
OBJECTIVE: To describe in vitro development of human embryos derived from an individual with a homozygous pathogenic variant in NLRP7 (19q13.42) and recurrent hydatidiform mole (HM), an autosomal recessive condition thought to occur secondary to an oocyte defect. METHODS: A patient with five consecutive HM pregnancies was genomically evaluated via next generation sequencing followed by controlled ovarian hyperstimulation, in vitro fertilization (IVF) with intracytoplasmic sperm injection, embryo culture, and preimplantation genetic screening. Findings in NLRP7 were recorded and embryo culture and biopsy data were tabulated as a function of parental origin for any identified ploidy error. RESULTS: The patient was found to have a pathogenic variant in NLRP7 (c.2810+2T>G) in a homozygous state. Fifteen oocytes were retrieved and 10 embryos were available after fertilization via intracytoplasmic sperm injection. Developmental arrest was noted for all 10 embryos after 144 hours in culture, thus no transfer was possible. These non-viable embryos were evaluated by karyomapping and all were diploid biparental; two were euploid and eight had various aneuploidies all of maternal origin. CONCLUSION: This is the first report of early human embryo development from a patient with any NLRP7 mutation. The pathogenic variant identified here resulted in global developmental arrest at or before blastocyst stage. Standard IVF should therefore be discouraged for such patients, who instead need to consider oocyte (or embryo) donation with IVF as preferred clinical methods to treat infertility.
Abortion, Habitual
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Aneuploidy
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Biopsy
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Blastocyst
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Diploidy
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Embryonic Development*
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Embryonic Structures*
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Female
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Fertilization
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Fertilization in Vitro*
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Genetic Testing
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Gestational Trophoblastic Disease*
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Humans
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Hydatidiform Mole
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In Vitro Techniques*
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Infertility
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Oocytes
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Parents
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Ploidies
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Pregnancy
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Sperm Injections, Intracytoplasmic