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JAMA Psychiatry Jun 2024
Topics: Humans; Obsessive-Compulsive Disorder; Male; Female; Diseases in Twins; Adult; Twins, Monozygotic; Twins, Dizygotic; Genetic Predisposition to Disease
PubMed: 38568562
DOI: 10.1001/jamapsychiatry.2024.0299 -
Journal of Orthopaedic Surgery and... Apr 2024The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully...
INTRODUCTION
The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully understood. While repetitive physical exercise-related stress is usually assumed to be the main risk factor for the occurrence of OCD, genetic predisposition could have an underestimated influence on the development of the disease.
CASE REPORT
We report a case of monozygotic twins with almost identical stages of bilateral osteochondrosis dissecans of the knee joint. In both patients, initially, a unilateral lesion occurred; despite restricted physical exercise, in the further course of the disease a lesion also developed on the contralateral side. While the lesion found most recently demonstrated an ongoing healing process at a 6-month follow-up, the other three lesions showed a natural course of healing under conservative treatment with significant clinical as well as radiological improvements after one year and complete consolidation in magnetic resonance imaging (MRI) after 2 years.
CONCLUSION
There could be a genetic component to the development of OCD, although this has not yet been proven. Based on a two-year MRI follow-up, we were able to show the self-limiting characteristics of juvenile osteochondrosis dissecans.
Topics: Humans; Knee Joint; Magnetic Resonance Imaging; Osteochondritis Dissecans; Osteochondrosis; Radiography; Twins, Monozygotic
PubMed: 38561825
DOI: 10.1186/s13018-024-04683-2 -
Stem Cell Research Jun 2024Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems...
Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems from point mutations in mitochondrial DNA (mtDNA), with key mutations being m.3460G > A, m.11778G > A, and m.14484 T > C. Fibroblasts from identical twins, sharing m.14484 T > C and m.10680G > A variants each with 70 % heteroplasmy, were used to generate iPSC lines. Remarkably, one twin, a LHON patient, displayed symptoms, while the other, a carrier, remained asymptomatic. These iPSCs offer a valuable tool for studying factors influencing disease penetrance and unravelling the role of m.10680G > A, which is still debated.
Topics: Humans; Optic Atrophy, Hereditary, Leber; Induced Pluripotent Stem Cells; Twins, Monozygotic; DNA, Mitochondrial; Male; Mitochondria; Female; Point Mutation; Adult
PubMed: 38552355
DOI: 10.1016/j.scr.2024.103406 -
Journal of Surgical Case Reports Mar 2024Studies in monozygotic (MZ) twins may help researchers elucidate the complex relationships between genetic and environmental factors on weight loss. We present a world...
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.
PubMed: 38549721
DOI: 10.1093/jscr/rjae192 -
Metabolites Mar 2024Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We...
Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy-Walker malformation, respiratory distress, and multiorgan dysfunctions. Through WGS, we identified two rare homozygous variants in both subjects, a pathogenic variant in (p.Arg565Trp) and a novel variant in (p.Glu910Val). These genes have been previously associated with autosomal recessive polymicrogyria and hypomyelinating neuropathy with/without contractures, respectively. The twins exhibited symptoms that overlapped with both of these conditions. The results of the untargeted metabolomics analysis revealed significant metabolic perturbations relating to neurodevelopmental abnormalities, kidney dysfunction, and microbiome. The significant metabolites belong to essential pathways such as lipids and amino acid metabolism. The identification of variants in two genes, combined with the support of metabolic perturbation, demonstrates the rarity and complexity of this phenotype and provides valuable insights into its underlying mechanisms.
PubMed: 38535312
DOI: 10.3390/metabo14030152 -
Med (New York, N.Y.) Apr 2024In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk...
BACKGROUND
In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk factors. Studies on monozygotic twins discordant for MS offer a unique way to reduce this complexity and reveal discrepant subsets.
METHODS
In this study, we analyzed B cell subsets in blood samples of monozygotic twins with and without MS using publicly available data. We verified functional characteristics by exploring the role of therapy and performed separate analyses in unrelated individuals.
FINDINGS
The frequencies of CXCR3 memory B cells were reduced in the blood of genetically identical twins with MS compared to their unaffected twin siblings. Natalizumab (anti-VLA-4 antibody) was the only treatment regimen under which these frequencies were reversed. The CNS-homing features of CXCR3 memory B cells were supported by elevated CXCL10 levels in MS cerebrospinal fluid and their in vitro propensity to develop into antibody-secreting cells.
CONCLUSIONS
Circulating CXCR3 memory B cells are affected by non-heritable cues in people who develop MS. This underlines the requirement of environmental risk factors such as Epstein-Barr virus in triggering these B cells. We propose that after CXCL10-mediated entry into the CNS, CXCR3 memory B cells mature into antibody-secreting cells to drive MS.
FUNDING
This work was supported by Nationaal MS Fonds (OZ2021-016), Stichting MS Research (19-1057 MS, 20-490f MS, and 21-1142 MS), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program grant agreement no. 882424, and the Swiss National Science Foundation (733 310030_170320, 310030_188450, and CRSII5_183478).
Topics: Humans; Multiple Sclerosis; Memory B Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Natalizumab; Receptors, CXCR3
PubMed: 38531361
DOI: 10.1016/j.medj.2024.02.013 -
NeuroImage. Clinical 2024Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus,...
OBJECTIVE
Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS.
METHODS
FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV.
RESULTS
54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003).
CONCLUSION
We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.
Topics: Humans; Adult; Female; Male; Twins, Monozygotic; Magnetic Resonance Imaging; Multiple Sclerosis; Middle Aged; Brain; Young Adult; Age of Onset; Organ Size
PubMed: 38522363
DOI: 10.1016/j.nicl.2024.103597 -
Cureus Feb 2024We analyzed multimodal retinal and choroidal imaging, including optical coherence tomography (OCT) and OCT angiography (OCTA), to assess differences and characterize...
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.
PubMed: 38516463
DOI: 10.7759/cureus.54557 -
Fa Yi Xue Za Zhi Feb 2024
Topics: Humans; Male; Genetic Markers; Twins, Monozygotic; Fathers
PubMed: 38500475
DOI: 10.12116/j.issn.1004-5619.2023.530702 -
BioRxiv : the Preprint Server For... Mar 2024Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection...
Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection indicating variants are acquired much earlier in life with unexplained initial growth spurts. Here we use fluctuating CpG methylation as a lineage marker to track stem cell clonal dynamics of hematopoiesis. We show, via the shared prenatal circulation of monozygotic twins, that weak selection conferred by stem cell variation created before birth can reliably yield clonal hematopoiesis later in life. Theory indicates weak selection will lead to dominance given enough time and large enough population sizes. Human hematopoiesis satisfies both these conditions. Stochastic loss of weakly selected variants is naturally prevented by the expansion of stem cell lineages during development. The dominance of stem cell clones created before birth is supported by blood fluctuating CpG methylation patterns that exhibit low correlation between unrelated individuals but are highly correlated between many elderly monozygotic twins. Therefore, clonal hematopoiesis driven by weak selection in later life appears to reflect variation created before birth.
PubMed: 38496542
DOI: 10.1101/2024.03.02.583106