Molar Tissue Research Articles

Twin Pregnancy Coexisting with Partial Mole and Normal Fetus: A Case Report

This case report highlights the rare occurrence of a twin pregnancy coexisting with a partial mole, presenting a unique set of challenges in management and outcome. A 20-year-old woman with primary subfertility conceived twins following ovulation induction, experiencing hyperemesis gravidarum and subsequently developing severe preeclampsia. Despite efforts to control her condition, termination of the pregnancy was necessary due to maternal safety concerns. Both twins, without anomalies, succumbed to early neonatal death. Histopathological examination revealed a partial mole. The case emphasizes the importance of vigilant monitoring and individualized treatment in such complex pregnancies, with a focus on maternal well-being. Continued follow-up is crucial to detect and manage potential gestational trophoblastic disease. This report underscores the need for informed decision-making and patient-centered care in managing twin pregnancies coexisting with molar tissue.

Impending thyroid storm caused by hydatidiform mole

Introduction: Thyroid storm is a rare but life-threatening endocrine emergency. It is an acute exaggerated clinical manifestation of thyrotoxic state. We report an impending thyroid storm caused by a hydatidiform mole in a 14-year-old girl. This paper intends to describe hyperthyroidism secondary to molar pregnancy highlighting the rare but essential evaluation of hyperthyroidism. Case: A 14-year-old girl was consulted by the obstetric division to evaluate and manage hydatidiform mole with suspected hyperthyroidism. She had frequent palpitations and tremors for 1 week ago. She also complained of nausea and vomiting 1 week before admission to the hospital. We found a Burch-Wartofsky score of 25, which was categorized as an impending thyroid storm. Laboratory results showed mild anemia, low thyroid stimulating hormone (TSH) levels, high free thyroxine (T4) levels, and markedly elevated beta-human chorionic gonadotropin (beta-hCG) levels, normal Thyroid-stimulating hormone receptor antibodies (TRAb). Other laboratory parameters are mediocre. The ECG results showed sinus tachycardia. A mole tissue biopsy of the uterus confirms the morphology of the hydatidiform mole. These findings established the diagnosis of Impending Thyroid Storm caused by a hydatidiform mole. Conclusion: A hydatidiform mole can cause thyroid storm because the hormone hCG has similar structure to TSH. Doctors should always estimate the possibility of hyperthyroidism in a molar pregnancy.

Predictors of surgical difficulty in upper third molar removal: a prospective cohort study.

Upper third molar (U3M) removal is a common surgical procedure. The aims of this study were to assess the patient-specific, radiological and surgical factors related to the difficulty of U3M removal, and to determine the incidence of intraoperative and postoperative complications. A prospective cohort study was carried out in adult patients undergoing U3M removal. Operative time, surgeon-reported difficulty and the Parant classification were used to assess extraction difficulty. Clinical, radiological and surgical factors were recorded to determine their relationship with surgical difficulty. A descriptive, bivariate and multivariate statistical analysis was carried out. A total of 250 patients were included. The mean operative time was 10.4 (±12.3) minutes, mean surgeon-reported difficulty was 3.2/10 (±2.3). The multivariate analysis showed greater impaction against the second molar and greater soft tissue and bony impaction to significantly increase operative time and surgeon-perceived difficulty. Additionally, surgeon experience was related to perceived difficulty. The overall incidence of intraoperative complications was 0.8%, and no postoperative events were recorded. Upper third molars in close relation with the roots of the adjacent second molar and with soft tissue and bony impaction are significantly more difficult to extract. Perceived difficulty was related to surgeon experience. This procedure appears to produce few intra- and postoperative complications.

Transient hyperthyroidism in a woman with hydatidiform mole: a case report on unusual clinical presentation and management

Background: Hydatidiform mole (HM) is a genetically abnormal conception involving abnormal growth of placental trophoblast. HM is sometimes accompanied by hyperthyroidism, a rare but potentially life-threatening complication requiring early detection and management. This study aimed to report a case of a woman with HM complicated by transient hyperthyroidism, as well as to analyze some possible pharmacological management before the evacuation of molar tissue. Case Presentation: A 45-year-old female was referred to Dr. Soetomo Hospital Surabaya with a chief complaint of vaginal bleeding, accompanied by nausea, vomiting, frequent heart palpitations, and hand tremors. The patient had been previously diagnosed with molar pregnancy but refused to undergo curettage. At presentation, physical examination suggested incompatible uterus size with the gestational age, and the vaginal toucher indicated non-palpable ballottement. Vesicles were observed in vaginal discharge. Laboratory findings revealed elevated β-HCG, decreased thyroid stimulating hormone (TSH), and increased free thyroxine (FT4) levels. Abdominal ultrasound exhibited the presence of uterine fibroid and a honeycomb appearance. The patient was then diagnosed with molar pregnancy accompanied by hyperthyroidism; however, Burch-Warsofsky’s (BW) score (25) suggested no thyroid crisis. Before undergoing suction curettage to evacuate the hydatidiform mole, the patient received perioperative treatment for thyrotoxicosis control using methimazole, propranolol, and dexamethasone. After the surgery, hCG levels were regularly followed up until the normal range was reached. Conclusion: Despite its rarity, hyperthyroidism might become a deadly complication in molar pregnancy. Perioperative treatment to stabilize thyroid levels is prominent to prevent a thyroid storm. Treatment choice depends on the time available for preoperative preparation, the severity of the thyrotoxicosis, and the impact of any current or previous therapies. However, β-blockers should always be used unless absolutely contraindicated. Follow-up of hCG level post-operatively is critical to identify a possible occurrence of gestational trophoblastic neoplasia (GTN).

SAT494 Impending Thyroid Storm during Pregnancy in a Patient with Gestational Trophoblastic Disease

Abstract Disclosure: R. Kulkarni: None. Z. Sibai: None. Background: Gestational trophoblastic disease (GTD) is a rare complication of pregnancy that arises due to abnormal proliferation of trophoblasts of the placenta. The incidence of GTD in the United States of America is about 110 to 120 per 100,000 pregnancies. Abnormal trophoblastic proliferation leads to higher than expected B-HCG levels compared to normal pregnancy. Since the beta subunit of β-hCG has similar structure to TSH, β-hCG stimulates TSH receptor and causes hyperthyroidism during pregnancy which can be asymptomatic, mild or it can lead to severe cases of thyroid storm. Clinical Case: A 19-year-old African American woman with no PMH, 8 weeks primigravida presented with complaints of nausea, abdominal pain and difficulty walking. Associated symptoms included blurry vision, excessive sweating, tremors and palpitations. Physical examination finding included sinus tachycardia and low BMIof 18.6kg/m2, bilateral hand tremors, weakness of bilateral lower extremities. Initial labs showed quantitative β-hCG level of 283,163(H) m(iU)/mL, TSH <0.010 (L) m(iU)/L , FT4 2.54 (H) ng/dL, negativeTSI and TPO Abs. Burch-Wartofsky Point Scale score was 35 suggestive of impending thyroid storm. Pelvic ultrasound showed intrauterine pregnancy with estimated gestation age of 7 weeks 3 days with findings suggestive of fetal demise. Patient underwent Dilatation and Curettage for suspected molarpregnancy. Final histopathological report of aborted specimen verified the diagnosis of partial molar pregnancy. Based on clinical history, physical finding and lab results, patient was diagnosed with gestational trophoblastic disease induced impending thyroid storm. Endocrinology initiated management with Propranolol 40 mg TID and Methimazole 10 mg daily withimprovement in her clinical symptoms in two days. One week follow up as an outpatient showed resolution of symptoms, normalization of free T4 and down trending β-hCG titers to 166 m(iU)/mL. Propranolol and methimazole were stopped. Conclusion:Gestational trophoblastic disease although a rare clinical entity, it is potentially a life-threatening condition. β-hCG is a glycoprotein, and its beta subunit is structurally similar to TSH, allowing it to bind to the TSH receptor and causing hyperstimulation of the thyroid follicular cells leading to various degrees of hyperthyroidism. GTD associated with significant high level of β-HCG, in rare cases can cause severe consequences like thyroid storm. Therefore, GTD should be considered as a differential diagnosis in patient’s presenting with sever thyrotoxicosis during pregnancy. The mainstay of management is evacuation of the molar pregnancy. In severe cases of hyperthyroidism, Beta blocker and thioamides can be considered for symptoms relief and to speed the recovery. Follow-up with serial quantitative β-hCG measurements is crucial to evaluate for persistent molar tissue. Presentation Date: Saturday, June 17, 2023

EP27.25: Enhanced myometrial vascularisation and retained molar tissue: a case report

EP27.25: Enhanced myometrial vascularisation and retained molar tissue: a case report

Molar pregnancy with a co-exist normal viable fetus and successful pregnancy outcome: a case report

Background: Co-existence of a hydatidiform mole with a normal fetus is extremely rare and is considered as a high risk pregnancy. Methods: It was an observational study conducted during July 2020 to march 2021 Case report: A 23 year old primigravida, referred with a diagnosis of 27 weeks pregnancy with gestational choriocarcinoma. She was booked patient. USG report at 9 weeks with a single gestational sac and single fetal pole. Her complains were lower abdominal pain and brownish vaginal discharge. Thoroughly evaluated the patient to exclude distal metastasis. Serum Beta HCG was 3,23,280 IU/L. USG and fetal MRI report were single graved fetus, no anomaly detected and a large hyper echogenic soft tissue mass (10*7cm) interposed with multiple tiny cystic spaces near to placenta. Diagnosis was 28 weeks pregnancy with partial mole and high rising β HCG level. Proper counseling, the pregnancy was continued as per the patient’s desire. The pregnancy was closely monitored with serial serum β HCG, and USG. Spontaneously labour pain start at 36 weeks pregnancy and delivered a live baby per vaginally at 36 weeks with near normal Apgar score. The placenta with molar tissue was sent for histopathological examination. The histopathologically confirmed partial mole with normal placenta. Beta HCG was 20,000 ml/L at 7 days and normal at 8 weeks after delivery. Close surveillance for 6 months. After 6 month follow-up, both mother and development of her baby are alright. Conclusion: The diagnosis, management and monitoring of this condition will remain challenging because of its rarity. Though the general trend is to terminate pregnancy with coexistent mole in anticipation of complications, under close surveillance, optimal outcomes can be achieved. Bangladesh Medical Res Counc Bull 2022; 48(3): 249-253

Laparoscopic management of an invasive mole combined with iatrogenic uterine perforation

ObjectiveHydatidiform mole is a common placental proliferative disease which is harmful to women's reproductive health. It is characterized by abnormal fertilization and subsequent trophoblastic proliferation. Invasive mole originates from hydatidiform mole, but its pathogenesis is still unclear. It has been reported that hydatidiform mole mainly develop with the uterine cavity. Invasive mole caused by iatrogenic uterine perforation is rarely reported. Here, we reported a rare case of invasive mole initially presented with uterine iatrogenic perforation after suction curettage. Case reportA 25-year-old nulliparous woman (gravida 1 para 0) who presented with acute hemoperitoneum was admitted to our hospital. Her clinical manifestation was mimicked by uterine iatrogenic perforation, and mole tissues were found on the left posterior wall of uterus. Laparoscopic management was performed to clear the lesions away thoroughly and repair the uterus. The operation was successful, and the reproductive function was preserved. The patient gave a birth to a healthy baby four years after the operation. ConclusionLaparoscopic minimally technique plays a very good therapeutic effect on invasive mole initially presented with iatrogenic uterine perforation.

Boring form of an invasive mole: case report and review of the literature

Gestational trophoblastic diseases include a heterogeneous group of pathologies due to abnormal trophoblast proliferation. These diseases are rare and most often have a good prognosis. Management recommendations are based mainly on expert opinions, such as those published in 2020 by the European Organisation for the Treatment of Trophoblastic Disease (EOTTD). They have a common name, but their origins, clinical characteristics and treatment differ. Hydatidiform moles correspond to villi with an excess of paternal genetic material and having a malignant potential, higher for complete Hydatidiform moles than for partial Hydatidiform moles Invasive mole is responsible for most cases of localized gestational trophoblastic neoplasia, occurring during pregnancy, within a variable period, but in most cases it is diagnosed after a molar pregnancy. Histological proof is sometimes difficult on curettage product, and must then take into account imaging and serum hCG levels. The overall cure rate is nearly 100% in low-risk patients and 90% in high-risk patients, since the advent of chemotherapy. In rare cases, the molar tissue crosses the thickness of the myometrium, the serosa and leads to hemoperitoneum associated with an acute abdomen as well as metastases, which is infrequently encountered in the invasive mole. The best course of treatment is chemotherapy (depending on the stage and the score with mono or poly chemotherapy) and in patients whose fertility is not in question, a hysterectomy can be performed. On the occasion of a clinical case, we will expose a dissecting form with an ovarian metastasis of an invasive mole. The treatment was successful. During the follow-up, she remained free of the disease without any sequelae.

Age prediction in sub-adults based on MRI segmentation of 3rd molar tissue volumes

PurposeOur aim was to investigate tissue volumes measured by MRI segmentation of the entire 3rd molar for prediction of a sub-adult being older than 18 years.Material and methodWe used a 1.5-T MR scanner with a customized high-resolution single T2 sequence acquisition with 0.37 mm iso-voxels. Two dental cotton rolls drawn with water stabilized the bite and delineated teeth from oral air. Segmentation of the different tooth tissue volumes was performed using SliceOmatic (Tomovision©). Linear regression was used to analyze the association between mathematical transformation outcomes of the tissue volumes, age, and sex. Performance of different transformation outcomes and tooth combinations were assessed based on the p value of the age variable, combined or separated for each sex depending on the selected model. The predictive probability of being older than 18 years was obtained by a Bayesian approach.ResultsWe included 67 volunteers (F/M: 45/22), range 14–24 years, median age 18 years. The transformation outcome (pulp + predentine)/total volume for upper 3rd molars had the strongest association with age (p = 3.4 × 10−9).ConclusionMRI segmentation of tooth tissue volumes might prove useful in the prediction of age older than 18 years in sub-adults.

Renal effects of hydatiform mole and choriocarcinoma

Molar pregnancy is an abnormal growth of trophoblastic tissue in the uterus. It can be either complete or partial. In complete moles, the development of the fetus is absent, while partial moles contain an abnormal gestational sac. Choriocarcinoma is a malignant form that arise from molar tissue. Hydatiform mole and choriocarcinoma are rare and complicated diseases with numerous pathological conditions that can lead to significant kidney damage. Proteinuria, nephrotic syndrome, preeclampsia, decreased glomerular filtration rate, interstitial inflammation, crescentic glomerulonephritis, and thrombosis of the renal veins are the commonly encountered renal disorders with these diseases. Early intervention and treatment during pregnancy minimize these risks and lessen the risk of chronic kidney disease or end-stage renal failure. A multidisciplinary team approach involving obstetricians, nephrologists, pathologists, gynecologists, and radiologists is necessary for optimal management.

The Role of Different Healing Abutment Sizes in Tissue Volume Preservation of Molar Sockets After Immediate Tooth Extraction and Implant Placement: A Multicenter Clinical Study.

To evaluate the role of different healing abutment designs in compensating for the buccolingual volumetric tissue change that occurs following flapless single-tooth immediate extraction placement in the molar area. Patients in need of extraction and replacement of a first or second molar in the mandible or maxilla were consecutively recruited. Immediately after extraction and implant placement, an abutment was connected. Five different types of abutments were randomly selected to be used for each case. The study population was divided into five categories according to abutment design: 5-mm diameter healing abutment (group 1); 6-mm diameter healing abutment (group 2); 7.5-mm diameter healing abutment (group 3); provisional restoration (group 4); and customized healing abutment (group 5). The buccopalatal dimension (BPD) was measured on the study casts at 1, 3, and 5 mm apical to the free gingival margin, and horizontal volumetric changes were compared between baseline and 2, 4, and 6 months. A total of 267 implants were inserted in 246 patients. The breakdown of placed implants for each group was as follows: 67 implants in group 1; 64 in group 2; 71 in group 3; 33 in group 4; and 32 in group 5. Changes in the mean horizontal ridge dimension were as follows. After 6 months in group 1, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 4.21 ± 0.158, 3.38 ± 0. 178 and 2.35 ± 0.178 mm. In group 2, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 3.16 ± 0.198, 2.56 ± 0.198, and 1.62 ± 0.198 mm. In group 3, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 2.53 ± 0.138, 2.16 ± 0.144, and 1.56 ± 0.144 mm. In group 4, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 1.11 ± 0.179, 1.23 ± 0.179, and 1.12 ± 0.179 mm. In group 5, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 0.25 ± 0.225, 0.30 ± 0.225, and 0.19 ± 0.225 mm. Mixed-effect regression and post hoc means comparisons were used to model the impact of the restoration technique, height of measurement, and time on BPD using a significance reference level of .05. Statistical analysis showed that the type of abutment, the height of measurement, and the time significantly influenced the BPD and that there were complex interaction effects between these variables. The observed volumetric soft tissue changes in the 6-month short-term follow-up appeared to vary based on the use of different healing abutment sizes that were connected to implants placed immediately after tooth extraction in the molar area. In particular, the use of a customized healing abutment resulted in preservation of the original horizontal dimension of the molar soft tissue.

Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis

Cranial neural crest cells are an evolutionary innovation of vertebrates for craniofacial development and function, yet the mechanisms that govern the cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Using the mouse molar as a model, we perform single-cell transcriptome profiling to interrogate the cell fate diversification of postmigratory cranial neural crest cells. We reveal the landscape of transcriptional heterogeneity and define the specific cellular domains during the progression of cranial neural crest cell-derived dental lineage diversification, and find that each domain makes a specific contribution to distinct molar mesenchymal tissues. Furthermore, IGF signaling-mediated cell-cell interaction between the cellular domains highlights the pivotal role of autonomous regulation of the dental mesenchyme. Importantly, we reveal cell-type-specific gene regulatory networks in the dental mesenchyme and show that Foxp4 is indispensable for the differentiation of periodontal ligament. Our single-cell atlas provides comprehensive mechanistic insight into the cell fate diversification process of the cranial neural crest cell-derived odontogenic populations.

MicroRNA Expression Profiling in Hydatidiform Mole for the Prediction of Postmolar GTN : MicroRNA Profile in Postmolar GTN.

Objectives: The primary aim of the study was to identify miRNAs that were differentially expressed between complete hydatidiform moles (CHMs) that turned out to be gestational trophoblastic neoplasia (GTN) [GTN moles] and CHMs that regressed spontaneously after evacuation [remission moles]. The secondary aim was to study the profiles of miRNA expressions in CHMs. Methods: A case-control study was conducted on GTN moles and remission moles. We quantitatively assessed the expression of 800 human miRNAs from molar tissues using Nanostring nCounter. Results: From a pilot study, 21 miRNAs were significantly downregulated in GTN moles compared to the remission moles. Five of them (miR-566, miR-608, miR-1226-3p, miR-548ar-3p and miR-514a-3p) were downregulated for >4 folds. MiR-608 was selected as a candidate for further analysis on 18 CHMs (9 remission moles and 9 GTN moles) due to its striking association with malignant formation. MiR-608 expression was slightly lower in GTN moles compared to the remission moles, that is, 2.22 folds change [p = 0.063]. Conclusion: We identified 21 miRNAs that were differentially expressed between GTN moles and remission moles suggesting that miRNA profiles can distinguish between the two groups. Although not reaching statistically significant, miR-608 expression was slightly lower in GTN moles compared to remission moles.

Invasive Mole of the Uterus: A Case Report

Invasive mole is a rare subgroup of gestational trophoblastic disease characterized by the invasion of molar tissue into the myometrium or uterine vasculature. In this paper, we report the third case of invasive mole described in the Malagasy literature. A 33-year-old woman was referred to the Soavinandriana Hospital, her complaint was persistent vaginal bleeding during 2 months, occurring at 3 months of pregnancy with biological anemia without hemodynamic repercussions. The human chorionic gonadotropin (HCG) level was 385,931 mIU/ml. A haemostasis hysterectomy was performed. Histological examination showed an enlarged uterus and endometrial cavity containing edematous chorionic villi with trophoblastic proliferation invading the myometrium. The diagnosis was an invasive mole, stage I, FIGO score 6. Chemotherapy was prescribed but was not honored. After 45 days of follow-up, the serum βHCG level decreased to 1803 mIU/ml, without clinical symptoms. The patient then lost sight. Persistent vaginal bleeding after pregnancy may be the only clinical symptom of an invasive mole and should raise suspicion. Histological examination establishes the diagnosis. As this is an unusual cause of vaginal bleeding, our case should remind physicians that when faced with this symptom, the possibility of an invasive mole should be considered in order to make an early diagnosis for less aggressive treatment.

Evaluation of the microbial, cytotoxic and physico-chemical properties of the stainless steel crowns used in pediatric dentistry

Preformed stainless steel crowns are used in pediatric dentistry to obtain full crown restoration of primary molar teeth. They are consider the best restoration in terms of durability and effectiveness. The purpose of this study is to evaluate microbial, cytological and physio-chemical properties to determine whereas stainless steel crown are biocompatible, safe for surrounding tissue and helpful in avoiding micro-organisms influence on the tooth tissue. Based on the results, it was determined that stainless steel crowns used in pediatric dentistry represent no cytotoxic risk to the surrounding tissues, have a low probability of developing hypersensitivity to the coronal material and also that their biological properties make them suitable to use in pediatric dentistry for the reconstruction of damaged primary molar tissue.

Application of next-generation sequencing to preimplantation genetic testing for recurrent hydatidiform mole patients

To study the application of next-generation sequencing on preimplantation genetic testing for recurrent hydatidiform mole patients. A total of ten recurrent hydatidiform mole patients aged 27-34years with a history of at least twice hydatidiform moles and no normal pregnancy were collected from 2019 to 2020. The diagnosis of hydatidiform mole type was clarified using short tandem repeat genotyping on products of conception, and whole-exome sequencing was applied for all patients and their partners. Seven recurrent hydatidiform mole patients with complete hydatidiform mole/partial hydatidiform mole type among previous hydatidiform mole tissues and no Pathogenetic/Likely pathogenetic/Uncertain significance variants in NLRP7/KHDC3L/MEI1/C11orf80 underwent a procedure of preimplantation genetic testing. Next-generation sequencing for analyzing the copy number variants and the numbers of heterozygous single nucleotide polymorphism was adopted to clarify the ploidy and parental origin of the embryo chromosomes in vitro. Embryos with biparental diploidy were selected for transfer. Seven patients have undergone the procedure of preimplantation genetic testing, and twenty-three embryos were obtained, among which 82.6% (n = 19) were identified transferrable and 17.4% (n = 4) were identified aneuploid. Two patients have delivered healthy babies and another is currently in the second trimester after transfer. Analyzing the copy number variants and the numbers of heterozygous single nucleotide polymorphism on the basis of next-generation sequencing can be utilized in the procedure of preimplantation genetic testing among part of recurrent hydatidiform mole patients. The current study is effective to reduce the occurrence of hydatidiform mole with improved clinical strategy, the advanced testing technology and analysis methods, as three of seven patients have conceived or delivered successfully.

P–553 Women with molar pregnancies have a genetic susceptibility to aneuploid miscarriages

Abstract Study question What causes non-molar miscarriages in women with one hydatidiform mole (HM)? Summary answer We found a higher rate of aneuploidies in the non-molar miscarriages of women with HM than in those from women with sporadic or recurrent miscarriages. What is known already Women with hydatidiform moles have higher rates of miscarriages and women with recurrent miscarriages have higher rates of moles than women from the general population. Study design, size, duration We retrieved archived formalin-fixed paraffin embedded tissues from non-molar miscarriages of patients with one HM and analyzed them for the presence of aneuploidies using single nucleotide polymorphism (SNP)-microarray. We next determined the meiotic origin of the aneuploidies by genotyping the aneuploid non-molar miscarriages along with the parental genomes using microsatellite markers. Participants/materials, setting, methods All participants and some of their partners provided written consent to participate in our study, agreed to a blood draw for genotyping analysis, and agreed for us to retrieve their molar and non-molar tissues from various histopathology laboratories for research purposes. Main results and the role of chance We demonstrate for the first time that patients with an HM and miscarriages are at higher risk for aneuploid miscarriages [83.3%, 95% confidence interval (CI): 0.653–0.944] than women with sporadic (51.5%, 95% CI: 50.3–52.7%, p value = 0.0003828) or recurrent miscarriages (43.8%, 95% CI: 40.7–47.0%, p value = 0.00002). Genotyping the aneuploid miscarriages and the parental genomes demonstrated that most of the aneuploidies originated from errors in maternal meiosis I or II. Limitations, reasons for caution We were able to retrieve only 30 non-molar miscarriages from women with one HM for analysis. Expanding such analysis to a larger and independent cohort of miscarriages from such patients will be important to validate our observations. Wider implications of the findings: Our data suggest common genetic female germline defects predisposing to HM and aneuploid non-molar miscarriages in some patients. Trial registration number Not applicable

Expressions of cytokeratin 14 and proliferating cell nuclear antigen in the Hertwig's epithelial root sheath of a Vps4b knockout mouse.

The effect of Vps4b gene mutation on the expressions of cytokeratin 14 (CK14) and proliferating cell nuclear antigen (PCNA) in the Hertwig's epithelial root sheath (HERS) is investigated. The bilateral mandibular tissues of mouse on postnatal days 5, 9, 11, 15, and 19 were removed. The mandibular first molar tissue sections were obtained after paraffin embedding. The CK14 and PCNA expressions in the epithelial root sheath of the normal mouse and Vps4b knockout mouse were compared through immunohistochemistry. On postnatal day 5, the normal mouse began to form HERS and had a strong positive PCNA expression in the HERS cells; on postnatal day 9, the HERS structure was continuous, and PCNA was positive in the HERS cells; on postnatal day 11, a small portion of HERS began to break, and PCNA was weakly positive in the HERS cells; on postnatal day 15, HERS continued to fracture; PCNA was weakly and positively expressed in the HERS cells on the root surface; on postnatal day 19, the tooth root reached normal physiological length, and PCNA was positively expressed in the HERS cells of the terminal part. Similar to the normal mouse, the gene knockout mouse also formed a HERS structure on postnatal day 5. However, HERS began to break on postnatal day 9. On postnatal day 19, only a few fragments of HERS were found on the root surface, and the root development was immature. Moreover, the expression intensity of PCNA in the gene knockout mouse was decreased. The Vps4b gene mutation may change the CK14 and PCNA expressions, leading to abnormal root development.

The genetics of recurrent hydatidiform moles in Mexico: further evidence of a strong founder effect for one mutation in NLRP7 and its widespread.

To investigate the frequency of a founder mutation in NLRP7, L750V, in independent cohorts of Mexican patients with recurrent hydatidiform moles (RHMs). Mutation analysis was performed by Sanger sequencing on DNA from 44 unrelated Mexican patients with RHMs and seven molar tissues from seven additional unrelated patients. L750V was present in homozygous or heterozygous state in 37 (86%) patients and was transmitted on the same haplotype to patients from different states of Mexico. We also identified a second founder mutation, c.2810+2T>G in eight (18.1%) patients, and a novel premature stop-codon mutation W653*. Our data confirm the strong founder effect for L750V, which appears to be the most common mutation in NLRP7. We also report on six healthy live births to five patients with biallelic NLRP7 mutations, two from spontaneous conceptions and four from donated ovum and discuss our recommendations for DNA testing and genetic counseling.