Short Tandem Repeat Polymorphism Analysis Research Articles

Single-nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis.

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three-allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single-nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three-allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

ABO blood type compatibility is not a risk factor for gestationaltrophoblastic neoplasia development from androgenetic completehydatidiform moles.

Complete hydatidiform moles (CHMs) are allografts to patients in terms of an androgenetic origin. Thus, some immunological reactions may be involved in the development of gestational trophoblastic neoplasia (GTN) from CHMs. This study aimed to evaluate the effect of ABO blood group on the prognosis of androgenetic CHMs. A total of 129 patients who were diagnosed as having CHMs based on multiplex short tandem repeat polymorphism analysis were included. The ABO blood types of molar tissues were determined by single-nucleotide polymorphisms in the ABO gene using a high-resolution melting assay. The incidence of GTN was compared based on ABO compatibility between the patients and their molar tissues. The overall incidence of GTN was 17.1% (22/129). Gestational trophoblastic neoplasia occurred in 10.8% (4/37), 14.8% (8/54), 22.2% (6/27), and 36.4% (4/11) of type O, A, B, and AB patients, respectively. Type AB patients tended to develop GTN compared with other blood type patients (P=.093). In ABO type of CHMs, GTN occurrence was not significantly different as it was 16.4% (10/64), 16.0% (8/50), and 22.2% (4/18) for types O, A, and B, respectively (P=.854). According to the ABO incompatibility between patients and molar tissues, GTN occurred in 19.1% (18/94) of the compatible cases and 11.4% (4/35) of the incompatible cases; the occurrence was not significantly different (P=.223). Patients with type AB tended to develop GTN. However, ABO compatibility between patients and molar tissues had no relationship with GTN occurrence.

Clinical application of short tandem repeat polymorphism analysis in the differential diagnosis of early hydatidiform mole and hydropic abortion

Objective: To determine the clinical differential diagnosis value of short tandem repeat polymorphism (STR) analysis in early hydatidiform moles (HMs) and non-molar gestations. Methods: Four hundred eighty-one patients with suspected HMs were examined using traditional pathology methods and STR analysis. The value of the STR method in distinguishing HMs from non-molar gestations was evaluated. Results: Among 481 patients with suspected HMs, 177 were diagnosed with HMs and 304 with non-molar gestations based on histopathologic examination. The STR genotypic results show that 151 patients were diagnosed with HMs, including 63 complete HMs and 88 partial HMs. Three hundred thirty patients were diagnosed with non-molar gestations, including 43 patients with chromosome abnormalities. Among 63 complete HMs, 56 were monosyllabic and 7 were dispermic. All 88 partial HMs were dispermic. The histopathologic diagnoses in 84 patients were not in agreement with STR analyses. Among the 84 cases, 29 were incorrectly diagnosed with non-molar gestations and the others were incorrectly diagnosed with HMs by histopathologic examinations. The chi-test result demonstrated that the two methods were quite different. Conclusion: STR polymorphism analysis is a rapid, simple, and accurate method that can be utilized for accurate diagnosis of early HMs and hydropic abortions.

Comparison between vacuum aspiration and forceps plus blunt curettage for the evacuation of complete hydatidiform moles

ObjectiveSuction curettage is recommended for molar evacuation rather than sharp curettage because of its safety. However, the superiority of suction curettage with respect to the incidence of gestational trophoblastic neoplasia (GTN) has not been reported. This study aimed to compare the efficacy and safety of two evacuation procedures, vacuum aspiration and forceps/blunt curettage, for complete hydatidiform moles (CHMs) to determine the differences between them. Materials and methodsPatients with androgenetic CHM determined by multiplex short tandem repeat polymorphism analysis were included in this observational cohort study. Patients underwent evacuation with forceps and blunt curettage (forceps group) before March 2013 and with vacuum aspiration (vacuum group) thereafter. GTN was diagnosed based on the International Federation of Gynecology and Obstetrics 2000 criteria. The incidence of GTN and other clinical parameters were compared. ResultsNinety-two patients were diagnosed with androgenetic CHM. The number of patients in the forceps and vacuum groups was 41 and 51, respectively. The incidence of GTN was 12.2% (5/41) and 13.7% (7/51) in the forceps and vacuum groups, respectively, which was not significantly different (P = 1, Fisher's exact test). No major adverse events, such as uterine perforation and blood transfusion, were noted in either group. The median surgery time was shorter in the vacuum group (16 min) than in the forceps group (25 min) (P = 0.05, Mann–Whitney U test). ConclusionThere were no differences in the incidence of GTN between the forceps and vacuum groups for androgenetic CHM. However, vacuum aspiration could have the advantage of a shorter surgery period. The use of vacuum aspiration for molar pregnancy seems to be safer. Therefore, we recommend suction curettage for the first evacuation of hydatidiform moles.

Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study.

The aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting. The prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs. Among 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test). Under the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN.

Elucidation of the developmental mechanism of ovarian mature cystic teratomas using B allele-frequency plots of single nucleotide polymorphism array data.

Ovarian mature cystic teratomas (MCTs) originate from post-meiotic germ cells. Conventional methods such as karyotyping or short tandem repeat-polymorphism analysis may be used to better classify MCTs, although such data would be insufficient. The aim of this study was to elucidate the origin of ovarian MCTs using B allele-frequency (BAF) plots of single nucleotide polymorphism array data. MCTs can be classified in terms of the zygosity of the centromeres and distal chromosome regions. We evaluated the zygosity of all chromosomes from 38 MCT specimens using BAF plot data. BAF plots were used to determine the homozygous and heterozygous regions over the whole genome. Theoretically, MCTs originated from the fusion of two ova (previously referred to as type V MCTs) should have a mixed pattern of centromeric zygosity, that is, a combination of heterozygous and homozygous regions in the centromeric regions. However, no MCTs in this study met this criterion. We identified 13 type I MCTs, 14 type II MCTs, and 11 type III MCTs. In addition, BAF plots facilitated the construction of recombination maps at the whole-genome level for type I and II MCTs. No crossover, especially in the short arms, contributed to the failure of meiosis I, resulting in type I MCTs. Crossover in all arms might assure the normal progress of meiosis in human oocytes. In conclusion, our findings indicate that BAF plots can elucidate the developmental mechanism of MCTs, and further serve as useful analytical tools for analyzing human oocyte meiosis, and related aberrations.

Complete hydatidiform moles are composed of paternal chromosomes and maternal mitochondria

Mitochondrial DNA (mtDNA) and genomic DNA are produced in separate subcellular compartments. Human mtDNA is transmitted via maternal transmission in general. Complete hydatidiform moles (CHMs) represent major trophoblastic diseases that are cytogenetically exceptional because the chromosomal genomic DNA is derived only from sperm cells, making them strikingly different from normal concepti. However, few reports have described the mtDNA-transmission pattern in hydatidiform moles. To evaluate mtDNA transmission in androgenetic CHMs, we compared the sequences of hypervariable regions in 16 trios sets of mtDNAs from maternal, paternal, and villous samples of androgenetic CHMs diagnosed by short tandem repeat-polymorphism analysis. All mtDNAs in androgenetic CHMs were maternally derived, in line with the general human inheritance pattern. Three maternal mtDNAs were heteroplasmic. The heterozygous status of maternal mtDNA was reflected in villous tissue, in which variants status was also heterozygous. CHMs are composed of paternal chromosomes and maternal mitochondria.

Primary Intraplacental Gestational Choriocarcinoma

Gestational choriocarcinoma is a highly malignant form of gestational trophoblastic tumors. Placental involvement of the tumor is exceedingly rare. We describe a case of intraplacental choriocarcinoma in a full-term placenta. Microscopically, there were sheets of highly pleomorphic trophoblasts invading the placenta, leaving isolated chorionic villi within the tumor. We utilized molecular genetic methods to determine the genotype of the tumor and compared it with that of the placenta. Short tandem repeat polymorphism analysis was performed on tumor and placental DNA macrodissected from unstained slides of formalin-fixed, paraffin-embedded tissue. The assay included polymerase chain reaction reactions of 10 polymorphic genetic loci. Comparing the polymorphic genetic markers of the tumor with the placenta revealed a complete match in the genotype of all loci examined. The results suggest that the choriocarcinoma originated from the current placenta sharing exactly the same genotype of multiple polymorphic markers. It also excludes a nongestational choriocarcinoma, which is of germ cell origin.

Pure XY gonadal dysgenesis and agenesis in monozygotic twins

To report a case of monozygotic twin sisters who had discordant gonadal dysgenesis although each had a normal 46,XY karyotype. Case report. University tertiary hospital. Seventeen-year-old twin sisters, one with gonadal agenesis and the other with pure gonadal dysgenesis followed by dysgerminoma. Blood samples were obtained for karyotyping and short tandem repeat polymorphism analysis (10 markers). Both patients underwent gonadectomy. Both sisters are well at time of report after gonadectomy for the sister with dysgerminoma and diagnostic laparoscope for the other. Dysgerminoma and atrophic ovarian stromal and tubal structures. Monozygotic twins can have discordant gonadal dysgenesis even though they are identical genetically.

Molecular characterization of inv dup del(8p): analysis of five cases.

We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity.

De novo trisomy 16p11.2-qter: Report of an infant

We report on a four-month-old girl with a de novo trisomy 16q [47,XX, +del(16)(p11.2).ish del(16)(p11.2)(wcp16+,D16Z2+,tel16q+, tel16p-)]. She had minor facial anomalies, limb anomalies, urogenital abnormalities, and severe cardiovascular defects. Autopsy confirmed left hypoplastic lung, total anomalous pulmonary venous drainage via coronary sinus, persistent left superior vena cava, patent ductus arteriosus, secundum atrial septal defect, bilateral hydronephrosis and hydroureters, uterus bicornis, and ovarian hypoplasia. Short tandem repeat polymorphism analysis indicated that the additional, structurally abnormal chromosome 16 was maternal in origin.