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BMC Medical Genomics May 2024Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are...
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.
Topics: Humans; Twins, Monozygotic; Myosin Heavy Chains; Male; Genetic Association Studies; Infant, Newborn; Phenotype; Cardiac Myosins; Aortic Aneurysm, Thoracic; Ductus Arteriosus, Patent; Female; Mutation; Aortic Dissection
PubMed: 38773466
DOI: 10.1186/s12920-024-01908-5 -
Clinical, Cosmetic and Investigational... 2024Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins...
INTRODUCTION
Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper extremity.
CASE PRESENTATION
Seven-year-old monozygotic twins presented to our department with a palpable, painless, and solid mass in the subcutaneous tissue of the right upper limb. A 1.5-cm diameter nodule was seen on the anterolateral aspect of the right upper extremity of the twins. The node was irregular in shape, and upon palpation, the patients reported no noticeable tenderness. Following the administration of local anesthesia, the twins underwent surgical procedure to excise the solid mass. Finally, they were diagnosed with pilomatricoma based on the clinical and histopathological features. Complete surgical resection followed by primary closure was performed. During a follow-up period of three years, there has been no recurrence observed in the twins.
CONCLUSION
We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper arm. Our findings underscore the requirement of considering genetic factors in the diagnosis and treatment of the rare conditions.
PubMed: 38765195
DOI: 10.2147/CCID.S455880 -
Research Square May 2024Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across...
Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.
PubMed: 38746362
DOI: 10.21203/rs.3.rs-4333635/v1 -
Molecular Genetics & Genomic Medicine May 2024Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20. (Review)
Review
BACKGROUND
Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20.
METHODS
We employed clinical observation and molecular genetic testing (SNP microarray), to study identical twin males with an unknown dysmorphic syndrome. We conducted a literature review of trisomy 20p and collated the clinical and molecular genetic findings on 20 affected subjects reported since 2000.
RESULTS
Identical twin males, whose prenatal course was complicated by a twin-to-twin transfusion, manifested profound language and neurocognitive delays as well as distinctive facial dysmorphisms when evaluated at 2 years of age. SNP microarray identified identical duplications of 20p13 with no other chromosomal aberrations. A literature survey of 20p trisomy syndrome identified 20 other examples of this condition reported since 2000, which we collated with 33 summarized by Sidwell et al. (2000). Within the combined total of 55 affected individuals, we found a distinctive clinical phenotype that provides insight on the effects of abnormal dosage of genes in 20p13. These loci include FAM110A (OMIM 611393), ANGPT4 (OMIM 603705), RSPO4 (OMIM 610573), PSMF1 (OMIM 617858), SNPH (OMIM 604942), SDCBP2 (OMIM 617358), FKBP1A (OMIM 186945), TMEM74B, C20orf202, and RAD21L1 (OMIM 619533). Gene profiling highlighted that syntaphilin (SNPH) is highly expressed in mammalian brain, where it is considered critical for mitochondrial transport in neuronal axons, and to directly influence axonal morphogenesis and function.
CONCLUSION
We propose that abnormal activity of syntaphilin engendered by the trisomy is primarily responsible for the language, neurocognitive, and gross motor delays reported in individuals with 20p trisomy. Additional studies, for example, characterization of cerebral organoids generated from affected patients may help to better understand this condition, and potentially suggest rational remedies to improve the lives of affected individuals and their families.
Topics: Humans; Male; Trisomy; Chromosome Duplication; Child, Preschool; Twins, Monozygotic; Polymorphism, Single Nucleotide
PubMed: 38738460
DOI: 10.1002/mgg3.2436 -
SA Heart Journal Apr 2024Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a...
Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.
PubMed: 38737401
DOI: 10.24170/21-1-6322 -
Biological Psychiatry Global Open... Jul 2024Development of synaptic activity is a key neuronal characteristic that relies largely on interactions between neurons and astrocytes. Although astrocytes have known...
BACKGROUND
Development of synaptic activity is a key neuronal characteristic that relies largely on interactions between neurons and astrocytes. Although astrocytes have known roles in regulating synaptic function and malfunction, the use of human- or donor-specific astrocytes in disease models is still rare. Rodent astrocytes are routinely used to enhance neuronal activity in cell cultures, but less is known about how human astrocytes influence neuronal activity.
METHODS
We established human induced pluripotent stem cell-derived neuron-astrocyte cocultures and studied their functional development on microelectrode array. We used cell lines from 5 neurotypical control individuals and 3 pairs of monozygotic twins discordant for schizophrenia. A method combining NGN2 overexpression and dual SMAD inhibition was used for neuronal differentiation. The neurons were cocultured with human induced pluripotent stem cell-derived astrocytes differentiated from 6-month-old astrospheres or rat astrocytes.
RESULTS
We found that the human induced pluripotent stem cell-derived cocultures developed complex network bursting activity similar to neuronal cocultures with rat astrocytes. However, the effect of NMDA receptors on neuronal network burst frequency (NBF) differed between cocultures containing human or rat astrocytes. By using cocultures derived from patients with schizophrenia and unaffected individuals, we found lowered NBF in the affected cells. We continued by demonstrating how astrocytes from an unaffected individual rescued the lowered NBF in the affected neurons by increasing NMDA receptor activity.
CONCLUSIONS
Our results indicate that astrocytes participate in the regulation of neuronal NBF through a mechanism that involves NMDA receptors. These findings shed light on the importance of using human and donor-specific astrocytes in disease modeling.
PubMed: 38706704
DOI: 10.1016/j.bpsgos.2024.100313 -
BMC Pregnancy and Childbirth May 2024To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived... (Comparative Study)
Comparative Study
Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.
OBJECTIVE
To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally.
METHODS
We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally.
RESULT
MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05).
CONCLUSION
Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.
Topics: Humans; Female; Pregnancy; Pregnancy, Twin; Reproductive Techniques, Assisted; Pregnancy Outcome; Retrospective Studies; Adult; Twins, Monozygotic; Chorion; Premature Birth; Twins, Dizygotic; Infant, Newborn; Placenta Previa
PubMed: 38698326
DOI: 10.1186/s12884-024-06521-z -
International Journal of Surgery Case... Jun 2024Posterior 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...
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.
PubMed: 38688154
DOI: 10.1016/j.ijscr.2024.109682 -
Journal of Atherosclerosis and... Apr 2024A twin study is a valuable tool for elucidating the acquired factors against lifestyle diseases such as dyslipidemia, diabetes mellitus, and obesity. We aimed 1. to...
AIM
A twin study is a valuable tool for elucidating the acquired factors against lifestyle diseases such as dyslipidemia, diabetes mellitus, and obesity. We aimed 1. to investigate the factors that affect low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in monozygotic (MZ) twins, and 2. to identify genes which expression levels changed in pairs with large differences in LDL-C or HDL-C levels.
METHODS
The registered database at the Center for Twin Research, Osaka University, containing 263 pairs of MZ twins, was analyzed. 1. The effects of smoking, exercise, nutritional factors, and anthropometric and biochemical parameters on LDL-C or HDL-C levels were examined in MZ twins. 2. RNA sequencing in the peripheral blood mononuclear cells of 59 pairs was analyzed for large differences of LDL-C or HDL-C groups.
RESULTS
1. The ΔLDL-C levels were significantly associated with an older age, the ΔTG levels, and ΔBMI. ΔHDL-C levels were associated with the ΔBMI, ΔTG, ΔTP, and ΔLDL-C levels. The HDL-C levels were affected by smoking and exercise habits. The intakes of cholesterol and saturated fatty acids were not associated with the LDL-C or HDL-C levels. 2. An RNA sequencing analysis revealed that the expression of genes related to the TLR4 and IFNG pathways was suppressed in accordance with the HDL-C levels in the larger ΔHDL-C group among the 59 pairs.
CONCLUSION
We identified the factors affecting the LDL-C or HDL-C levels in monozygotic twins. In addition, some types of inflammatory gene expression in peripheral blood mononuclear cells were suppressed in accordance with the HDL-C levels, thus suggesting the importance of weight management and exercise habits in addition to dietary instructions to control the LDL-C or HDL-C levels.
PubMed: 38684403
DOI: 10.5551/jat.64882 -
Genes Apr 2024The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of...
The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age-75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.
Topics: Humans; Female; Aged; Male; Aged, 80 and over; Aging; Twins, Dizygotic; Twins, Monozygotic; Gene Expression
PubMed: 38674429
DOI: 10.3390/genes15040495