Clinical utility of selective molecular genotyping for diagnosis of partial hydatidiform mole; a retrospective study from a regional trophoblastic disease unit

2014 ◽  
Vol 67 (11) ◽  
pp. 980-984 ◽  
Author(s):  
Rosemary A Fisher ◽  
Anna Tommasi ◽  
Dee Short ◽  
Baljeet Kaur ◽  
Michael J Seckl ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Hydatidiform Mole ◽  
Placental Tissue ◽  
Management Approach ◽  
Parental Origin ◽  
Definite Diagnosis ◽  
Maternal Tissue ◽  
Molecular Genotyping ◽  
Increased Risk ◽  
Technical Issues

AimsHydatidiform moles (HMs) are genetically abnormal conceptions, associated with increased risk of gestational trophoblastic neoplasia. Diagnosis is usually based on histopathological criteria but in a minority definitive histological diagnosis is not possible; in such cases molecular genotyping may be diagnostic. This study describes the clinical usefulness of such an approach.MethodsCases in which central histology review demonstrated abnormal villous morphological features insufficient for definite diagnosis of partial HM (PHM) (‘favour PHM’ or ‘PHM not excluded’) underwent molecular genotyping of villous and maternal tissue, using short tandem repeats, to determine ploidy and parental origin of the placental tissue.ResultsOf 251 cases with non-diagnostic morphological villous abnormalities, molecular investigation was not possible in 14 (6%; limited material or technical issues). Overall, 124 (49%) were triploid including 71/86 (85%) of those morphologically favouring PHM, and 53/165 (32%) of those favouring non-molar miscarriage. Of 85 cases of triploidy in whom sufficient material was available, 84 had an additional paternal contribution. Single cases of digynic triploidy, tetraploid PHM and two mosaic conceptions were also identified. Twenty-three non-molar diploid cases (21%) exhibited trisomy.ConclusionsMolecular genotyping allows definitive diagnosis of PHM for cases in which specialist histopathology review remains equivocal. While this approach provides definite diagnosis it is considerably more expensive than a pragmatic management approach of human chorionic gonadotrophin surveillance in all such cases.

scholarly journals Molecular Analysis of Nondisjunction in Mice Heterozygous for a Robertsonian Translocation

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1219-1224
Author(s):  
Lara A Underkoffler ◽  
Laura E Mitchell ◽  
A Russell Localio ◽  
Shannon M Marchegiani ◽  
Justin Morabito ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Robertsonian Translocation ◽  
Metacentric Chromosome ◽  
Paternal Age ◽  
Chromosome 7 ◽  
Parental Origin ◽  
Molecular Genotyping ◽  
Factors Influencing ◽  
Meiotic Nondisjunction ◽  
Acrocentric Chromosomes

Abstract A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%.Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters.There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction.Strain background did not play an appreciable role in nondisjunction frequency.The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males.The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males. These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals.

scholarly journals Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 544
Author(s):  
Tien-Chi Huang ◽  
Kung-Chao Chang ◽  
Jen-Yun Chang ◽  
Yi-Shan Tsai ◽  
Yao-Jong Yang ◽  
...  
Keyword(s):  
Maternal Effect ◽  
Hydatidiform Mole ◽  
Placental Tissue ◽  
Differentially Methylated Region ◽  
Normal Birth ◽  
Maternal Effect Genes ◽  
Common Etiology ◽  
Artificial Abortion ◽  
Secondary Dmr ◽  
Placental Mesenchymal Dysplasia

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

scholarly journals Analysis of Management Approach to Newborn Care of Infants Delivered to COVID-19 Positive Mothers at Five Tertiary Care Centers in the UAE over a 7 Month Period 

2021 ◽  
Author(s):  
Monika Kaushal ◽  
Yamuna Tulasi ◽  
Ayush Kaushal ◽  
Aditya Rakhecha ◽  
Rafiq Memon ◽  
...  
Keyword(s):  
Observational Study ◽  
Tertiary Care ◽  
Newborn Care ◽  
Retrospective Observational Study ◽  
Management Approach ◽  
Post Discharge ◽  
Formula Milk ◽  
Increased Risk ◽  
Care Practices ◽  
Tertiary Care Centers

Abstract ObjectivesTo assess newborn care practices, clinical characters and risks of mother to child transmission during rooming in and breastfeeding in infants born to mothers with COVID-19.DesignRetrospective observational study.Participants5 Tertiary care centers located in the UAE. Infants born to mothers diagnosed with COVID-19 at the time of delivery, born between April 1st and October 30th 2020.MethodsIn this retrospective observational study, we analyzed the newborn care practices in various tertiary care hospitals and the rate of transmission of SARS-CoV-2 from mother to infant (vertical or horizontal) while rooming in, breastfeeding and post discharge. Results40 infants were born to mothers with COVID-19 at the time of delivery. One infant tested positive for SARS-CoV-2 after birth and had respiratory symptoms and fever. 23 of the well infants were roomed in during their hospital stay and were breastfed. In 8 cases, the mother and baby were separated and isolated from the time of birth till discharge. 95% of the discharged infants were rooming in with mothers, 45% of the infants were exclusively breastfed and 55% were on mixed feeding (breast milk and formula milk) at the follow-up. None of the infants developed significant health issues or symptoms attributable to SARS-CoV-2.ConclusionThe risk of mother to infant transmission of COVID-19 in the perinatal period is very low. Our study reaffirms the AAP guidelines that rooming in and breastfeeding of newborns born to COVID-19 positive mothers is safe without an increased risk of transmission by following mandated safety precautions.

scholarly journals Parental Origin and Phenotype of Triploidy in Spontaneous Abortions: Predominance of Diandry and Association with the Partial Hydatidiform Mole

2000 ◽  
Vol 66 (6) ◽  
pp. 1807-1820 ◽  
Author(s):  
Michael V. Zaragoza ◽  
Urvashi Surti ◽  
Raymond W. Redline ◽  
Elise Millie ◽  
Aravinda Chakravarti ◽  
...  
Keyword(s):  
Hydatidiform Mole ◽  
Parental Origin ◽  
Spontaneous Abortions ◽  
Partial Hydatidiform Mole

Platelet glycoprotein Ibα Kozak polymorphism is associated with an increased risk of ischemic stroke

Blood ◽  
2001 ◽  
Vol 98 (1) ◽  
pp. 36-40 ◽  
Author(s):  
Ross I. Baker ◽  
John Eikelboom ◽  
Elizabeth Lofthouse ◽  
Nicole Staples ◽  
Vahid Afshar-Kharghan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Tandem Repeats ◽  
Surface Expression ◽  
Variable Number ◽  
Platelet Glycoprotein ◽  
Postal Code ◽  
Stroke Subtype ◽  
Increased Risk ◽  
Conventional Risk Factors

Abstract Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibα. Three polymorphisms have been described in GP Ibα (Kozak T/C polymorphism, variable number of tandem repeats [VNTR], and the human platelet antigen 2a [HPA-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ibα interaction. This study investigated whether these polymorphisms are candidate genes for first-ever ischemic stroke. A hospital-based case-control study was conducted of 219 cases of first-ever ischemic stroke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were classified, the prevalence of conventional risk factors was recorded, and blood was collected to perform genotyping analysis for Kozak C or T alleles, VNTR, and HPA-2a/b. It was found that the Kozak T/C genotype was over-represented in the stroke group (32.2%) compared with controls (22.8%) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.54; P < .03), and the association was still present even after adjusting for conventional risk factors. There was a trend in the increased prevalence of HPA-2a/b in stroke patients (15%) compared with controls (9.9%) (adjusted OR, 1.8; 95% CI, 0.94-3.4; P = .07). No associations were seen with the VNTR polymorphism or with any of the polymorphisms with stroke subtype. It was concluded that the Kozak T/C polymorphism, which is associated with an increase in platelet GP Ibα surface expression, is an independent risk factor for first-ever ischemic stroke.

Clinicopathologic characterization and outcomes for patients with renal medullary carcinoma: Results from the National Cancer Database.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 456-456
Author(s):  
Harras B. Zaid ◽  
Robert Houston Thompson ◽  
Bradley C. Leibovich ◽  
William P. Parker ◽  
Brian Addis Costello ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Systemic Therapy ◽  
Multivariable Analysis ◽  
Medullary Carcinoma ◽  
Management Approach ◽  
National Cancer Database ◽  
Clinicopathologic Features ◽  
Cox Regression Analysis ◽  
Renal Medullary Carcinoma ◽  
Increased Risk

456 Background: Renal medullary carcinoma (RMC) is a rare, aggressive malignancy for which relatively limited characterization exists to date. We evaluated clinicopathologic features, treatment patterns, and variables associated with outcomes for patients with RMC. Methods: We reviewed the National Cancer Database to identify patients diagnosed with RMC between 1998-2012. Overall survival (OS) was estimated using the Kaplan-Meier method. Clinicopathologic features associated with all-cause mortality (ACM) were assessed using Cox regression analysis. Results: We identified 153 patients with RMC, comprising approximately 0.04% of renal malignancies during this time period. Median age at diagnosis for RMC was 24 years (IQR 20, 31). The majority of RMC patients were black (135; 88%), male (108; 71%), and presented with unilateral, right-sided tumors (101; 66%). Notably, nearly half (72; 48.9%) presented with metastatic disease. A total of 92 (64.3%) patients underwent radical nephrectomy (RN), and 2 (1.3%) were treated with partial nephrectomy. Pathologic stage at nephrectomy was ≤pT2 in 30 patients (32.6%), pT3 in 43 (46.7%), pT4 in 7 (7.6%), and N+ in 50 (55.6%). Of the patients who underwent RN, 60 (65.2%) received multimodal therapy (MMT), including radiation (3; 3.3%), systemic therapy (49; 53.3%), and radiation + systemic therapy (8; 8.7%). Of the 59 patients who did not undergo surgical resection, the majority (46; 77.8%) presented with M1 disease. Median OS was 7.8 months for the entire RMC cohort, with 1- and 3-year OS of 34% and 11%, respectively. Notably, median OS for patients presenting with M1 and M0 disease was 5.2 months versus 11.2 months, respectively (p< 0.01). On multivariable analysis, treatment with RN (HR 0.40; p=0.003) or RN+MMT (HR 0.44; p<0.001) were associated with decreased ACM, whereas the presence of metastatic disease at diagnosis remained associated with an increased risk of ACM (HR 1.74; p=0.02). Conclusions: The prognosis for patients with RMC is dismal, with a median OS under 8 months. Further studies, including the development of novel therapies, are needed to establish the optimal multimodal management approach for these patients.

scholarly journals Chasing perfection: validation and polishing strategies for telomere-to-telomere genome assemblies

2021 ◽  
Author(s):  
Arang Rhie ◽  
Ann Mc Cartney ◽  
Kishwar Shafin ◽  
Michael Alonge ◽  
Andrey Bzikadze ◽  
...  
Keyword(s):  
Genome Assembly ◽  
Tandem Repeats ◽  
Hydatidiform Mole ◽  
Segmental Duplications ◽  
Sequencing Technologies ◽  
Oxford Nanopore ◽  
Human Genome Assembly ◽  
Long Read ◽  
Genome Assemblies ◽  
Oxford Nanopore Technologies

Abstract Advances in long-read sequencing technologies and genome assembly methods have enabled the recent completion of the first Telomere-to-Telomere (T2T) human genome assembly, which resolves complex segmental duplications and large tandem repeats, including centromeric satellite arrays in a complete hydatidiform mole (CHM13). Though derived from highly accurate sequencing, evaluation revealed that the initial T2T draft assembly had evidence of small errors and structural misassemblies. To correct these errors, we designed a novel repeat-aware polishing strategy that made accurate assembly corrections in large repeats without overcorrection, ultimately fixing 51% of the existing errors and improving the assembly QV to 73.9. By comparing our results to standard automated polishing tools, we outline common polishing errors and offer practical suggestions for genome projects with limited resources. We also show how sequencing biases in both PacBio HiFi and Oxford Nanopore Technologies reads cause signature assembly errors that can be corrected with a diverse panel of sequencing technologies

scholarly journals Wide Field Imaging and Angiography

2017 ◽  
pp. 32-37
Keyword(s):  
Age Related Macular Degeneration ◽  
Peripheral Retina ◽  
Management Approach ◽  
Wide Field ◽  
Autofluorescence Imaging ◽  
Retinal Periphery ◽  
Age Related ◽  
Increased Risk ◽  
Field Imaging ◽  
Wide Field Imaging

The recently developed wide-field imaging systems (WIS) enable 200 degrees imaging of retina by just one shot and angiographic and autofluorescence imaging of retinal periphery. In addition to facilitating the detection of retinal pathologies, WIS revealed the importance of lesions in retinal periphery and peripheral nonperfusion areas invisible by standard angiography. The novel finding of utmost importance for diabetic retinopathy (DR) patients was the 3 fold increased risk of progression assessed for peripheral DR lesions compared to that in the posterior pole. Detection of peripheral nonperfusion areas in DR or retinal vein occlusion cases with refractory macular edema altered the management approach. On the other hand by means of WIS new terms have been brought into the era like peripheral vascular leakage whose relevance and importance are unknown for retinal vascular diseases. In age-related macular degeneration, a disease known to affect the macula, WIS proved the effect on peripheral retina documented by both angiographies and also peripheral autofluorescence. In diseases known to affect peripheral retina like uveitis, degenerative myopia, etc. WIS further contributes to the detection of additional pathologies. WIS enabled documentation of retinal periphery and thus seems to change the treatment modality and probably clinical classification of unknown or treatment-refractory pathologies in retinal diseases where we mainly focused on macula always.

scholarly journals Telomere-to-telomere assembly of a complete human X chromosome

2019 ◽  
Author(s):  
Karen H. Miga ◽  
Sergey Koren ◽  
Arang Rhie ◽  
Mitchell R. Vollger ◽  
Ariel Gershman ◽  
...  
Keyword(s):  
Human Genome ◽  
X Chromosome ◽  
Satellite Dna ◽  
Tandem Repeats ◽  
Reference Genome ◽  
De Novo ◽  
Hydatidiform Mole ◽  
Segmental Duplications ◽  
High Coverage ◽  
Current Reference

After nearly two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist 1,2. The remaining gaps include ribosomal rDNA arrays, large near-identical segmental duplications, and satellite DNA arrays. These regions harbor largely unexplored variation of unknown consequence, and their absence from the current reference genome can lead to experimental artifacts and hide true variants when re-sequencing additional human genomes. Here we present a de novo human genome assembly that surpasses the continuity of GRCh38 2, along with the first gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome 3, we reconstructed the ∼2.8 megabase centromeric satellite DNA array and closed all 29 remaining gaps in the current reference, including new sequence from the human pseudoautosomal regions and cancer-testis ampliconic gene families (CT-X and GAGE). This complete chromosome X, combined with the ultra-long nanopore data, also allowed us to map methylation patterns across complex tandem repeats and satellite arrays for the first time. These results demonstrate that finishing the human genome is now within reach and will enable ongoing efforts to complete the remaining human chromosomes.

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