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Monozygotic twins share the same genotype; however, they can be phenotypically discordant on various traits. Studying discordant monozygotic twins allows the investigation of differences in associations between symptoms and psychopathological risk factors, controlled for shared genetic liability. The network approach to psychopathology suggests that depressive symptoms, along with risk and protective factors (e.g., cognition, daily activities), form a complex system of mutually interacting components. We compared monozygotic twins discordant for lifetime depression on their respective extended networks of depressive symptoms, cognitive functions and daily activities (intellectual, physical, social), and evaluated if these networks differ in their associations between variables and in the role of each variable within the network. Regularized partial correlations investigated the networks' composition in 147 monozygotic twin pairs discordant for depression from the Danish Twin Registry. Affected twins had stronger overall associations within their network of depressive symptoms, cognitive functions and daily activities than their unaffected co-twins, while the importance of the network components' associations did not differ between the co-twins. In affected twins, decreased frequency in experiencing happiness had the strongest association with remaining variables (i.e., the most influence in activating other network elements). Also, variables from different groups were significantly associated (e.g., loneliness with delayed memory, pessimism with low social activities, verbal learning with intellectual activities). In unaffected twins, both mood symptoms and cognitive functions were important, but between-groups associations were quasi-absent. These results suggest that external events affecting the ability to feel happiness likely trigger the psychopathological process (depression network activation), independently from the genetic predisposition to depression.
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BACKGROUND: Monozygotic (MZ) twins are believed to arise from the fission of a single fertilized embryo at different stages. Monochorionic MZ twins, who share one chorion, originate from the splitting of the inner cell mass (ICM) within a single blastocyst. In the classic model for dichorionic MZ twins, the embryo splits before compaction, developing into two blastocysts. However, there are a growing number of ART cases where a single blastocyst transfer results in dichorionic MZ twins, indicating that embryo splitting may occur even after blastocyst formation. OBJECTIVE AND RATIONALE: For monochorionic MZ twins, we conducted a comprehensive analysis of the cellular mechanisms involved in ICM splitting, drawing from both ART cases and animal experiments. In addition, we critically re-examine the classic early splitting model for dichorionic MZ twins. We explore cellular mechanisms leading to two separated blastocysts in ART, potentially causing dichorionic MZ twins. SEARCH METHODS: Relevant studies including research articles, reviews, and conference papers were searched in the PubMed database. Cases of MZ twins from IVF clinics were found by using combinations of terms including 'monozygotic twins' with 'IVF case report', 'ART', 'single embryo transfer', or 'dichorionic'. The papers retrieved were categorized based on the implicated mechanisms or as those with unexplained mechanisms. Animal experiments relating to MZ twins were found using 'mouse embryo monozygotic twins', 'mouse 8-shaped hatching', 'zebrafish janus mutant', and 'nine-banded armadillo embryo', along with literature collected through day-to-day reading. The search was limited to articles in English, with no restrictions on publication date or species. OUTCOMES: For monochorionic MZ twins, ART cases and mouse experiments demonstrate evidence that a looser ICM in blastocysts has an increased chance of ICM separation. Physical forces facilitated by blastocoel formation or 8-shaped hatching are exerted on the ICM, resulting in monochorionic MZ twins. For dichorionic MZ twins, the classic model resembles artificial cloning of mouse embryos in vitro, requiring strictly controlled splitting forces, re-joining prevention, and proper aggregation, which allows the formation of two separate human blastocysts under physiological circumstances. In contrast, ART procedures involving the transfer of a single blastocysts after atypical hatching or vitrified-warmed cycles might lead to blastocyst separation. Differences in morphology, molecular mechanisms, and timing across various animal model systems for MZ twinning can impede this research field. As discussed in future directions, recent developments of innovative in vitro models of human embryos may offer promising avenues for providing fundamental novel insights into the cellular mechanisms of MZ twinning during human embryogenesis. WIDER IMPLICATIONS: Twin pregnancies pose high risks to both the fetuses and the mother. While single embryo transfer is commonly employed to prevent dizygotic twin pregnancies in ART, it cannot prevent the occurrence of MZ twins. Drawing from our understanding of the cellular mechanisms underlying monochorionic and dichorionic MZ twinning, along with insights into the genetic mechanisms, could enable improved prediction, prevention, and even intervention strategies during ART procedures. REGISTRAITON NUMBER: N/A.
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BACKGROUND: Autism spectrum disorder (ASD) is a childhood-onset complex neurodevelopmental disorder characterized by problems with communication and social interaction and restricted, repetitive, stereotyped behavior. The prevalence of ASD is one in 36 children. The genetic architecture of ASD is complex in spite of its high heritability. To identify the potential candidate genes of ASD, we carried out a comprehensive genetic study of monozygotic (MZ) twins concordant or discordant for ASD. METHODS: Five MZ twins and their parents were recruited for the study. Four of the twins were concordant, whereas one was discordant for ASD. Whole exome sequencing was conducted for the twins and their parents. The exome DNA was enriched using Twist Human Customized Core Exome Kit, and paired-end sequencing was performed on HiSeq system. RESULTS: We identified several rare and pathogenic variants (homozygous recessive, compound heterozygous, de novo) in ASD-affected individuals. CONCLUSION: We report novel variants in individuals diagnosed with ASD. Several of these genes are involved in brain-related functions and not previously reported in ASD. Intriguingly, some of the variants were observed in the genes involved in sensory perception (auditory [MYO15A, PLEC, CDH23, UBR3, GPSM2], olfactory [OR9K2], gustatory [TAS2R31], and visual [CDH23, UBR3]). This is the first comprehensive genetic study of MZ twins in an Indian population. Further validation is required to determine whether these variants are associated with ASD.
Subject(s)
Autism Spectrum Disorder , Exome Sequencing , Twins, Monozygotic , Humans , Autism Spectrum Disorder/genetics , Twins, Monozygotic/genetics , Male , Female , Child , Diseases in Twins/genetics , Child, PreschoolABSTRACT
Background: This article reports a case of neonatal incontinentia pigmenti onset in only one male monozygotic twin with characteristic skin lesions after birth followed by severe cerebrovascular lesions. Case presentation: A male infant, the first of monozygotic twins, was born with multiple yellow pustules all over his body, repeated new herpes at different sites during the course of the disease, aggravated by fusion, warty crusts, and hyperpigmentation; biopsy pathology suggested eosinophilic spongiform edema of the skin. Peripheral blood eosinophils were significantly elevated, and brain magnetic resonance imaging revealed diffuse multiple cystic and lamellar abnormal signal areas in the left frontal and parietal lobes. On day 30, the infant showed neurological symptoms, such as poor response and apnea, and an emergency cranial computed tomography scan revealed abnormal changes in the left cerebral hemisphere and bilateral cerebellum. After admission, he was given a potassium permanganate bath and topical mupirocin for 1 month, and the skin abnormalities improved. He was treated with mechanical ventilation and vasoactive drugs for 2 days after the cerebrovascular accident, and died the same day after the parents chose hospice care. No deletion variants or point mutations were detected in subsequent genetic tests, and chromosomal copy number variation tests revealed different degrees of chimeric duplications and deletions in different regions of chromosomes Y and 3. The parents were healthy, and his twin brother had normal growth and development with no abnormalities at multiple follow-up visits. Conclusion: Neonatal incontinentia pigmenti in only one male monozygotic twin is extremely rare and the genetic diagnosis is challenging. Awareness of the combined cerebrovascular lesions needs to be enhanced, and potential prevention and treatment methods need to be explored to improve the prognosis.
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Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine.
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We report on genetic and environmental modulation of social cognition abilities and brain volume correlates in two monozygotic twins (Twin1 and Twin2) with genetically confirmed myotonic dystrophy-type1 who grew up in different environmental settings. They both underwent neuropsychological assessment (i.e., Intelligent Quotient [IQ], theory of mind, emotion recognition tests), and MRI scanning to evaluate regional brain volumetrics compared to 10 gender and sex-matched healthy controls. Against a normal IQ level in both patients, Twin1 was more impaired in emotional processing and Twin2 in cognitive aspects of social cognition. Both patients showed grey matter (GM) atrophy in Brodmann Areas 23/31 (BA23/31) and BA7 bilaterally, while Twin2 showed additional GM loss in right BA46. Both patients showed a similar pattern of white matter atrophy involving the thalamus, basal ganglia, and uncinate fasciculus. White matter atrophy appeared to be mostly driven by genetics, while grey matter volumes appeared associated with different impairments in social cognition and possibly modulated by environment.
Subject(s)
Brain , Magnetic Resonance Imaging , Myotonic Dystrophy , Neuropsychological Tests , Phenotype , Twins, Monozygotic , Humans , Myotonic Dystrophy/genetics , Myotonic Dystrophy/pathology , Myotonic Dystrophy/diagnostic imaging , Brain/diagnostic imaging , Brain/pathology , Male , Female , Adult , Atrophy/pathology , Gray Matter/pathology , Gray Matter/diagnostic imaging , Middle Aged , White Matter/diagnostic imaging , White Matter/pathology , Social CognitionABSTRACT
BACKGROUND: Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype-phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins. METHODS: The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype-phenotype correlation of MYH11. RESULTS: The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006). CONCLUSION: This study expands the mutational spectrum of MYH11 and provides new insights into the genotype-phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.
Subject(s)
Genetic Association Studies , Myosin Heavy Chains , Twins, Monozygotic , Humans , Twins, Monozygotic/genetics , Myosin Heavy Chains/genetics , Male , Infant, Newborn , Phenotype , Cardiac Myosins/genetics , Aortic Aneurysm, Thoracic/genetics , Ductus Arteriosus, Patent/genetics , Female , Mutation , Aortic Dissection/geneticsABSTRACT
Twin gestation in the mare is undesirable and can have disastrous consequences. As in many cases, the key to success in twin management lies in a thorough follow-up and accurate recording of clinical findings in the pre-breeding examination. A pregnancy diagnosis in the mobility phase is imperative for a good outcome in the event of twin reduction. If a twin gestation is not diagnosed during this early pregnancy stage, several other procedures exist for managing post-fixation twins (>16 days) with varying degrees of success. Most twin pregnancies are the result of multiple ovulations (dizygotic twins). However, monozygotic twins are also sporadically diagnosed, due to the increasing number of transferred in vitro produced equine embryos. In these cases, the most optimal treatment strategy still needs to be determined. This review provides an overview of the various twin reduction techniques described with the expected prognosis as well as of some less reported techniques with their results. In addition, physiological events and the reduction techniques are demonstrated to the user in virtual 3-dimensional illustrations.
Subject(s)
Pregnancy Reduction, Multifetal , Animals , Female , Pregnancy , Horse Diseases/therapy , Horse Diseases/diagnosis , Horses , Pregnancy Reduction, Multifetal/veterinary , Pregnancy, Twin , Pregnancy, AnimalABSTRACT
INTRODUCTION AND IMPORTANCE: Posterior cruciate ligament (PCL) tears are not as frequent as anterior cruciate ligament (ACL) tears. They are rare as an isolated injury and more commonly occur in a multi-ligament-injured knee. We reported a case of rupture of PCL in monozygotic twins. CASE PRESENTATION: A 19-year-old female presented with giving away of her left knee since 4 months ago. She fell from stairs previously. Physical examination demonstrated positive posterior drawer test. Magnetic resonance imaging showed ruptured PCL and lateral meniscal tear. Two months later, her identical twin, also a 19-year old-female, fell from the stairs and complained of giving away. Physical examination showed positive posterior drawer test. Magnetic resonance imaging demonstrated ruptured PCL and lateral meniscal tear. Both patients underwent arthroscopic-assisted PCL reconstruction using gracilis, semitendinosus, and peroneus tendon graft. At one year of follow-up, there were no graft failures. The twins had satisfactory outcome measured by Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). Both were athletes prior to their injury and they returned to sport. CLINICAL DISCUSSION: Although it has never been reported before, this report shows that patients may have genetic predisposition to the incidence of PCL rupture. This is likely because of heritable factors, such as biomechanical, anatomic, anthropometric, and neuromuscular traits. A family history of PCL tear may increase the risk of a PCL tear. Further studies are recommended to examine genetic variants as a risk factor for PCL tears and other knee disorders. CONCLUSIONS: Multiple variables may lead to the increased risk of these twins: the combination of improper neuromuscular control, genetic factors, and possibly hormonal factors contributed to their PCL injuries. Further history exploration, lab tests, and genetic analysis should be done to determine the variables. Both patients returned to sports protocol testing and returned to sports one year postoperatively.
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Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins. Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents. Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population. Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.
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This study examined brain functional connectivity (FC) changes associated with possible anomalous interactions between sensorily isolated monozygotic (MZ) twins. Brain FC was estimated using the Steady State Visual Evoked Potential-Event Related Partial Coherence (SSVEP-ERPC) methodology. Five twin pairs served twice as participants, with an average interval between sessions of 67 days. In each recording session, one twin, the Sender, viewed a randomized set of 50 general images and 50 personally relevant images, while the other twin, the Receiver, viewed a static personally relevant image for the entire duration of the session. Images appeared on the Sender screen for 1.0 s, with the interval between successive images varied randomly between 4.0 and 8.0 s. Receiver FC changes were calculated based on the appearance times of the images as viewed by the Sender. It was hypothesized that anomalous interactions would be indicated by statistically significant Receiver FC changes when those changes are determined using the Sender image appearance times. For each twin serving as Receiver, FC components were separately analyzed for the 50 general and the 50 personal images, yielding 38 observations (19 twin pairs by 2 conditions). The hypothesis was confirmed in that 11 of the 38 observations yielded statistically significant Receiver FC increases or decreases at the p < 0.01 level only when trials were synchronized to the Sender image appearance times. Overall, this effect was significant at the p = 4 × 10-8 Df = 175. To the best of our knowledge, this is the first study reporting statistically significant FC changes indicative of anomalous interactions between two sensorily isolated individuals.
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Background: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially pave the way for novel therapeutic approaches. Methods: We examined the apolipoprotein E genotype and ApoE-levels, lipid profiles, and the correlation with cognition in 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected, AT), their unaffected co-twins (high-risk, HR), and twins with no personal or family history of affective disorder (low-risk, LR). Results: The APOE genotype was not associated with affective disorders. No significant group differences in ApoE levels were found between the three risk groups. Post hoc analysis group-wise comparisons showed higher ApoE levels in the AT than HR twins and in the concordant AT twin pairs relative to the discordant twin pairs. Within the discordant twin pairs, higher ApoE levels were observed in the affected twins (AT = 39.4 mg/L vs. HR = 36.8 mg/L, p = 0.037). Limitations: The present study could benefit from a larger sample size. We did not assess dietary habits. Conclusions: The results did not support our main hypothesis. However, exploratory post hoc analysis suggests a role for plasma ApoE and triglycerides in affective disorders. Future research is needed.
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Studies in monozygotic (MZ) twins may help researchers elucidate the complex relationships between genetic and environmental factors on weight loss. We present a world first of MZ twins who have undergone the single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) procedure who have identical weights 3 years post-operatively. Two MZ twin 49-year-old females were assessed preoperatively and were indicated for the SADI-S procedure. They underwent surgery in 2020 by the same surgical team. Three years later post-operatively they had identical weights of 62 kg (and a BMI of 23) and %EWL of 126 and 124% respectively. SADI-S is a novel bariatric procedure for morbid obesity. Studies have found concordant epigenetic patterns in patients who have undergone bariatric surgery as well as MZ twins who have hypocaloric diets. Genetics exert a strong influence in weight management. Surgical management as well as a collaborative multidisciplinary approach is beneficial in supporting long lasting weight loss in bariatric surgery.
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We analyzed multimodal retinal and choroidal imaging, including optical coherence tomography (OCT) and OCT angiography (OCTA), to assess differences and characterize variations in the retinal and choroidal structure and microvasculature between healthy monozygotic twins without ocular or systemic pathology over a five-year period. Retinal imaging of both subjects revealed normal age-related changes. There was up to an 11% difference in OCT and OCTA variables within the subjects, both at baseline and at five years, and there was up to an 18% difference in OCT and OCTA parameters between the subjects for both time points. Larger changes in subfoveal choroidal thickness and foveal avascular zone area were observed. Our observations suggest that the parafoveal superficial capillary plexus, choroidal vascularity index, central subfield thickness, retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness may be more heavily influenced by genetic, rather than environmental, factors. In contrast, subfoveal choroidal thickness and the foveal avascular zone area may be more heavily influenced by environmental factors. The environmental impact on retinal and choroidal structure and microvasculature is increasingly important to characterize, as such imaging parameters are being explored as potential biomarkers of systemic disease. These differences, as seen in these identical twin subjects, may be important considerations in supporting the security of biometric identifiers.
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PURPOSE: To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs. METHODS: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age-Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE-BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis. RESULTS: Twenty-nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2-4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3-4) versus the other being unaffected (AREDS 1). The within-pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418-0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE-BrM complex volume. RPE-BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172-0.688, p < 0.01). CONCLUSION: A substantial proportion of monozygotic twin pairs are discordant with regard to age-related macular degeneration phenotype. RPE-BrM complex volume associated with age and intermediate and late AMD.
Subject(s)
Bruch Membrane , Diseases in Twins , Macular Degeneration , Retinal Pigment Epithelium , Tomography, Optical Coherence , Twins, Monozygotic , Humans , Twins, Monozygotic/genetics , Tomography, Optical Coherence/methods , Female , Male , Aged , Retinal Pigment Epithelium/pathology , Retinal Pigment Epithelium/diagnostic imaging , Bruch Membrane/pathology , Macular Degeneration/diagnosis , Macular Degeneration/genetics , Diseases in Twins/diagnosis , Diseases in Twins/genetics , Aged, 80 and over , Finland/epidemiology , Middle AgedABSTRACT
BACKGROUND: The present study aimed to explore the maternal and perinatal risks in cases of monozygotic twins (MZT) following frozen-thawed embryo transfer (FET). METHODS: All twin births that were conceived following FET from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China were retrospectively reviewed. The exposure variable was twin type (monozygotic and dizygotic). The primary outcome was the incidence of neonatal death while secondary outcomes included hypertensive disorders of pregnancy, gestational diabetes, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, weight discordance, stillbirth, birth defects, pneumonia, respiratory distress syndrome, necrotizing enterocolitis, and neonatal jaundice. Analysis of the outcomes was performed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The causal mediation analysis was conducted. A doubly robust estimation model was used to validate the results. Kaplan-Meier method was used to calculate survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model. RESULTS: Of 6101 dizygotic twin (DZT) and 164 MZT births conceived by FET, MZT showed an increased risk of neonatal death based on the multivariate logistic regression models (partially adjusted OR: 4.19; 95% CI, 1.23-10.8; fully adjusted OR: 4.95; 95% CI, 1.41-13.2). Similar results were obtained with the doubly robust estimation. Comparing MZT with DZT, the neonatal survival probability was lower for MZT (P < 0.05). The results were robust in the sensitivity analysis. Females with MZT pregnancies exhibited an elevated risk of preterm premature rupture of the membranes (adjusted OR: 2.42; 95% CI, 1.54-3.70). MZT were also associated with higher odds of preterm birth (prior to 37 weeks) (adjusted OR: 2.31; 95% CI, 1.48-3.67), low birth weight (adjusted OR: 1.92; 95% CI, 1.27-2.93), and small for gestational age (adjusted OR: 2.18; 95% CI, 1.21-3.69) in the fully adjusted analyses. The effect of MZT on neonatal death was partially mediated by preterm birth and low birth weight (P < 0.05). CONCLUSIONS: This study indicates that MZT conceived by FET are related to an increased risk of neonatal death, emphasizing a potential need for comprehensive antenatal surveillance in these at-risk pregnancies.
Subject(s)
Fetal Membranes, Premature Rupture , Twins, Monozygotic , Female , Humans , Infant, Newborn , Pregnancy , China , Embryo Transfer/adverse effects , Embryo Transfer/methods , Perinatal Death , Placenta , Premature Birth/epidemiology , Premature Birth/etiology , Retrospective StudiesABSTRACT
AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.
Subject(s)
Aniridia , Corneal Opacity , Twins, Monozygotic , WAGR Syndrome , Wilms Tumor , Humans , Female , Twins, Monozygotic/genetics , WAGR Syndrome/genetics , Aniridia/genetics , Aniridia/complications , Wilms Tumor/genetics , Wilms Tumor/complications , Infant , Corneal Opacity/genetics , Anterior Eye Segment/abnormalities , Anterior Eye Segment/diagnostic imaging , Eye Abnormalities/genetics , Eye Abnormalities/diagnostic imaging , Eye Abnormalities/complications , Diseases in Twins/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/complicationsABSTRACT
BACKGROUND: The condition of monozygotic, monochorionic triplet fetuses with a pair of conjoined twins is extremely rare (close to one in a million births), presents challenges in its management, and with poor prognosis. CASE REPORT: We report a case of monochorionic diamniotic triplet pregnancy, ultrasound at 14 weeks shows a pair of conjoined thoracopagus fetuses, sharing heart, liver, and umbilical cord, in addition to omphalocele. The third fetus, without malformations, presents signs of early heart failure compatible with twin-to-twin transfusion syndrome. It was decided to carry out expectant management where at 18 weeks, intrauterine death of the three fetuses occurs. An abortion is performed by hysterotomy. CONCLUSIONS: The treatment in these cases is discussed, three management options have been proposed: expectant management, selective reduction of the conjoined fetuses, or termination of the pregnancy. A review of the literature found only 12 cases with this combination of pathologies, in which only 3 normal fetuses (25%) survived and none of the conjoined twins survived. To our knowledge, this case is the first of a monochorionic triplet pregnancy with conjoined fetuses complicated with early twin-to-twin transfusion.
Subject(s)
Fetofetal Transfusion , Pregnancy, Triplet , Twins, Conjoined , Female , Pregnancy , Humans , Fetofetal Transfusion/complications , Fetal Death/etiology , Fetus/abnormalitiesABSTRACT
Monozygotic (MZ) twins are theoretically genetically identical. Although they are revealed to accumulate mutations after the zygote splits, discriminating between twin genomes remains a formidable challenge in the field of forensic genetics. Single-nucleotide variants (SNVs) are responsible for a substantial portion of genetic variation, thus potentially serving as promising biomarkers for the identification of MZ twins. In this study, we sequenced the whole genome of a pair of female MZ twins when they were 27 and 33 years old to approximately 30 × coverage using peripheral blood on an Illumina NovaSeq 6000 Sequencing System. Potentially discordant SNVs supported by whole-genome sequencing were validated extensively by amplicon-based targeted deep sequencing and Sanger sequencing. In total, we found nine bona fide post-twinning SNVs, all of which were identified in the younger genomes and found in the older genomes. None of the SNVs occurred within coding exons, three of which were observed in introns, supported by whole-exome sequencing results. A double-blind test was employed, and the reliability of MZ twin discrimination by discordant SNVs was endorsed. All SNVs were successfully detected when input DNA amounts decreased to 0.25 ng, and reliable detection was limited to seven SNVs below 0.075 ng input. This comprehensive analysis confirms that SNVs could serve as cost-effective biomarkers for MZ twin discrimination.