Female Monozygotic Twins Research Articles

Fabry disease in female monozygotic twins with complex intronic haplotype variants: a case report

BackgroundFabry disease is an X-linked lysosomal storage disease caused by the impairment of α-galactosidase A. The complex intronic haplotype (CIH) variants, located in promoter and intronic regulatory lesions, has been found in patients with classical forms of Fabry disease. We present a case of Fabry disease in female monozygotic twins exhibiting the CIH mutation and classical manifestations.Case presentationA 61-year-old woman with a history of stroke, carotid artery occlusion, hypertrophic cardiomyopathy, and chronic kidney disease was referred to the nephrology clinic for management of her chronic kidney disease. Her monozygotic twin sister also presented with hypertrophic cardiomyopathy, atrial flutter, carotid stenosis, and proteinuria. Clinical symptoms and a comprehensive family history strongly suggested the presence of Fabry disease. Genetic analysis revealed the presence of 5 variants within a complex intronic haplotype (CIH): c.−10 C > T, c.369 + 990 C > A, c.370 − 81_370–77delCAGCC, c.640–16 A > G, and c.1000–22 C > T. We conducted a review of the patient’s previous kidney biopsy findings, which demonstrated the presence of lamellated inclusion bodies in electron microscopy. Remarkably, both the monozygotic twin sister and her son exhibited the same genetic mutation. Enzyme replacement therapy was initiated for the patient. Her kidney function decreased throughout a thorough 2-year follow-up period, while there was a slight decrease in the left ventricular mass index.ConclusionsThis is the first reported case of female monozygotic twins with the CIH variants representing cardiac, cerebrovascular, and renal manifestations suggestive of Fabry disease.

Unprecedented report: First female monozygotic twins as carriers of Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by premature aging resulting from an autosomal mutation in the LMNA gene. This article presents a groundbreaking instance of the first female monozygotic twins affected by HGPS, originating from Brazil, highlighting the exceptional nature of this case.

Bilateral Peters' anomaly, aniridia and Wilms tumour (WAGR syndrome) in monozygotic twins.

This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). 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. 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. 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.

Fabry disease in female monozygotic twins with a complex intronic haplotype mutation: A case report

Fabry disease in female monozygotic twins with a complex intronic haplotype mutation: A case report

Technical strategy for monozygotic twin discrimination by single-nucleotide variants.

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 33years 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 0.25ng, and reliable detection was limited to seven SNVs below 0.075ng input. This comprehensive analysis confirms that SNVs could serve as cost-effective biomarkers for MZ twin discrimination.

Prenatal dispositions and genetic analysis of monozygotic female twins with suprasellar cysts and hydrocephalus: A case report

IntroductionWe present a unique case of monozygotic female twins with virtually identical clinical and radiological presentations of supratentorial hydrocephalus and cystic formations from the suprasellar cistern.DiscussionEvaluating genetic predispositions and prenatal exposures is crucial for hydrocephalus in twins. Familial cases imply a genetic contribution to the development of these anomalies, including chromosomal abnormalities and specific variants linked to arachnoid cyst formation in various syndromes. Extensive genetic analyses found no pathogenic variants in the twins. Prenatal exposure to anti-epileptic medication was known during pregnancy and may be associated with fetal abnormalities, but not central nervous system (CNS) malformations, and was therefore not considered the cause of the condition in the twins. The twins presenting simultaneously with hydrocephalus caused by suprasellar cysts (SAC) underwent a two-step surgical management: initial ventriculoperitoneal shunt (VPS) placement followed by fenestration. Postoperative imaging showed cyst reduction, but a secondary VPS was necessary in both cases.ConclusionGenetic analysis is less likely to identify a monogenic etiology in non-syndromic cases of SACs, which are assumed to be multifactorial. There is no established evidence linking a teratogenic effect of anti-epileptic drugs to CNS malformations. Moreover, the surgical treatment of this complex condition constitutes a point of discussion.

Is There a Causal Relationship between Physical Activity and Bone Microarchitecture? A Study of Adult Female Twin Pairs.

The reasons for the association between physical activity (PA) and bone microarchitecture traits are unclear. We examined whether these associations were consistent with causation and/or with shared familial factors using a cross-sectional study of 47 dizygotic and 93 monozygotic female twin pairs aged 31-77 years. Images of the nondominant distal tibia were obtained using high-resolutionperipheral quantitative computed tomography. The bone microarchitecture was assessed using StrAx1.0 software. Based on a self-completed questionnaire, a PA index was calculated as a weighted sum of weekly hours of light (walking, light gardening), moderate (social tennis, golf, hiking), and vigorous activity (competitive active sports) = light + 2 * moderate + 3 * vigorous. We applied Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) to test whether cross-pair cross-trait associations changed after adjustment for within-individual associations. Within-individual distal tibia cortical cross-sectional area (CSA) and cortical thickness were positively associated with PA (regression coefficients [β] = 0.20 and 0.22), while the porosity of the inner transitional zone was negatively associated with PA (β = -0.17), all p < 0.05. Trabecular volumetric bone mineral density (vBMD) and trabecular thickness were positively associated with PA (β = 0.13 and 0.14), and medullary CSA was negatively associated with PA (β = -0.22), all p ≤ 0.01. Cross-pair cross-trait associations of cortical thickness, cortical CSA, and medullary CSA with PA attenuated after adjustment for the within-individual association (p = 0.048, p = 0.062, and p = 0.028 for changes). In conclusion, increasing PA was associated with thicker cortices, larger cortical area, lower porosity of the inner transitional zone, thicker trabeculae, and smaller medullary cavities. The attenuation of cross-pair cross-trait associations after accounting for the within-individual associations was consistent with PA having a causal effect on the improved cortical and trabecular microarchitecture of adult females, in addition to shared familial factors. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Steroid-resistant nephrotic syndrome associated with certain SGPL1 variants in a family: Case report and literature review.

Steroid-resistant nephrotic syndrome (SRNS) is a clinical syndrome characterized by the lack of response to standard steroid therapy, usually progressing to end-stage renal disease. We reported two cases of female identical twins with SRNS caused by SGPL1 variants in one family, reviewed the relevant literature, and summarized their clinical phenotypes, pathological types, and genotypic characteristics. Two cases of nephrotic syndrome caused by SGPL1 variants were admitted to Tongji Hospital, affiliated with Tongji Medical College of Huazhong University of Science and Technology. Their clinical data were retrospectively collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. Related literature published in PubMed, CNKI, and Wan fang databases was reviewed. We described two Chinese identical twin girls with isolated SRNS due to compound heterozygous variants in the SGPL1 (intron4 c.261 + 1G > A and intron12 c.1298 + 6T > C). The patients were followed up for 60.0 months and 53.0 months, respectively, having no extra-renal manifestations. They all died due to renal failure. A total of 31 children with SGPL1 variants causing nephrotic syndrome (including the reported two cases) were identified through a literature review. These two female identical twins were the first reported cases of isolated SRNS caused by SGPL1 variants. Almost all homozygous and compound heterozygous variants of SGPL1 had extra-renal manifestations, but compound heterozygous variants in the intron of SGPL1 may have no obvious extra-renal manifestations. Additionally, a negative genetic testing result does not completely rule out genetic SRNS because the Human Gene Mutation Database or ClinVar is constantly being updated.

Quadruplets: Risks, Outcomes and a Set of Four/Twin Research Reviews and a Lawsuit: Antenatal Corticosteroids and Twins’ Neonatal Outcomes; Fathers of Twins; Doppelgängers and Similarity; Monozygotic Co-Twin Difference in Asymmetric Pigmented Paravenous Chorioretinal Atrophy/In the News: Opposite-Sex Twin Holocaust Survivors; Twin Models at Gucci; Twins With Different Fathers; Reunited Twins Enter Same Convent; Death of a Twin Soldier During Training;

Quadruplets are at elevated physical risks at prenatal, perinatal, and postnatal levels, relative to twins. A brief review of this area is followed by discussion of a female quadruplet with three co-quadruplet brothers. Next, several timely twin research reports are examined. The topics include antenatal corticosteroids and twins' neonatal outcomes, the meaning of fatherhood in families with twins, what doppelgängers (look-alikes) reveal about physical and behavioral similarity, and monozygotic (MZ) co-twin discordance for asymmetric pigmented paravenous chorioretinal atrophy. A lawsuit involving alleged cheating on a medical school examination by identical twins is also reviewed. General interest stories cover opposite-sex twin Holocaust survivors, twin models at a Gucci fashion show, twins with different fathers, reunited female twins who entered the same convent, the death of an MZ female twin soldier during training, and the surgical separation of conjoined twins in Brazil.

Variable disease manifestations and metabolic management within a single family affected by ornithine transcarbamylase deficiency

We report on a family with ornithine transcarbamylase (OTC) deficiency, an X-linked urea cycle disorder, with variable disease severity and tailored management strategies based on each family member's biochemical profile and clinical presentation. Our primary patient is a female monozygotic twin who presented to medical care at 10 months of age with acute liver failure, gastrointestinal symptoms, altered mental status, hypoglycemia, and hyperammonemia. The patient's older brother, known to have hemizygous OTC deficiency, died at 8 months of age from cardiac arrest after complications secondary to his diagnosis. Despite her family history, manifestation of symptoms of heterozygous (partial) OTC deficiency went unrecognized by multiple providers based on misconceptions regarding a female's risk for X-linked disease. Despite barriers related to the family's low socioeconomic status, follow-up care by a multidisciplinary metabolic care team, including moderate protein restriction and nitrogen scavenger therapy, led to positive outcomes for the patient. Her twin sister and mother are also heterozygous for variants in OTC and remain controlled on moderate protein restriction. This case illustrates the importance of genotyping all individuals with genetic risk factors for OTC deficiency and the variability in disease manifestation that necessitates tailored treatment approaches for individuals with partial OTC deficiency.

Reared-Apart and Reunited: Extraordinary Dynamics/Twin Research Reviews: Twin Bereavement and Lifespan Associations; Identifying Novel Mutations in Twins; Parenting Premature Multiples; Conjoined Twins in Cross-Cultural Context/In the News: Madeline Albright, Mother of Twins, Passes Away; Identical Twin Songwriters Compose New Musical; Visually Impaired Twin Skiers; Identical Twin Brothers Undergo Heart Transplants; Naming the Genain Quadruplets

The focus of this article is on insights gained from the extraordinary dynamics that took place between a pair of reunited monozygotic female twins from Greece. Topics include visualizing the co-twin prior to meeting, the unique love and attraction between the twins, a mother's response to discovering her child's cotwin and the challenges posed by insufficient kinship categories. The following section of this article surveys four recent twin research reports. They include Bereavement and Lifespan Associations; Novel Mutations in Twins; Parenting Premature Multiples; and Conjoined Twins. The final part of this article presents interesting and informative news about twins from popular sources. The topics covered are the passing of Madeline Albright (Secretary of State and mother of twins); identical twin songwriters; visually impaired twin and sibling skiiers; identical twin brothers who both received heart transplants; and the naming of the Genain quadruplets.

Different epilepsy course of a novel AHDC1 mutation in a female monozygotic twin pair

PurposeDe novo truncating mutations of AHDC1 gene cause Xia-Gibbs Syndrome (XGS), characterized by developmental delay, hypotonia, speech disturbances, sleep apnea. Seizures have been reported, yet no studies have depicted the epilepsy characteristics and outcome. MethodsWe describe the clinical features of a pair of Caucasian monozygotic female twins affected by severe epilepsy and presenting the same de novo AHDC1 mutation detected by whole exome sequencing. ResultsThey were concordant with respect to seizure onset and type mimicking Lennox-Gastaut syndrome as well as initial EEG features, but differed in terms of epilepsy prognosis (complete seizure freedom on valproate/lamotrigine versus ongoing daily refractory seizures despite multiple drug combinations). ConclusionOur findings suggest that patients with Xia-Gibbs Syndrome may exhibit Lennox-Gastaut-like features and that even the same AHDC1 mutation can be poorly predictive of epilepsy prognosis.

Different epilepsy course of a novel AHDC1 mutation in a female monozygotic twin pair

Different epilepsy course of a novel AHDC1 mutation in a female monozygotic twin pair

Personality traits, mental abilities and other individual differences: Monozygotic female twins raised apart in South Korea and the United States

Twins reared apart are rare, especially twins raised in different countries and cultures. This report documents the behavioral, physical, and medical similarities and differences of monozygotic female cotwins, raised separately by an adoptive family in the United States and the biological family in South Korea. Similarities were evident in personality, self-esteem, mental health, job satisfaction and medical life history, consistent with genetic influence found by the Minnesota Study of Twins Reared Apart and related studies. An overall twin correlation across thirty-eight measures was r = 0.95, p < .001. In contrast with previous research, the twins' general intelligence and non-verbal reasoning scores showed some marked differences. Adding these cases to the psychological literature enhances understanding of genetic, cultural, and environmental influences on human development.

Nucleic Acid-Sensing and Interferon-Inducible Pathways Show Differential Methylation in MZ Twins Discordant for Lupus and Overexpression in Independent Lupus Samples: Implications for Pathogenic Mechanism and Drug Targeting.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune inflammatory disease with genomic and non-genomic contributions to risk. We hypothesize that epigenetic factors are a significant contributor to SLE risk and may be informative for identifying pathogenic mechanisms and therapeutic targets. To test this hypothesis while controlling for genetic background, we performed an epigenome-wide analysis of DNA methylation in genomic DNA from whole blood in three pairs of female monozygotic (MZ) twins of European ancestry, discordant for SLE. Results were replicated on the same array in four cell types from a set of four Danish female MZ twin pairs discordant for SLE. Genes implicated by the epigenetic analyses were then evaluated in 10 independent SLE gene expression datasets from the Gene Expression Omnibus (GEO). There were 59 differentially methylated loci between unaffected and affected MZ twins in whole blood, including 11 novel loci. All but two of these loci were hypomethylated in the SLE twins relative to the unaffected twins. The genes harboring these hypomethylated loci exhibited increased expression in multiple independent datasets of SLE patients. This pattern was largely consistent regardless of disease activity, cell type, or renal tissue type. The genes proximal to CpGs exhibiting differential methylation (DM) in the SLE-discordant MZ twins and exhibiting differential expression (DE) in independent SLE GEO cohorts (DM-DE genes) clustered into two pathways: the nucleic acid-sensing pathway and the type I interferon pathway. The DM-DE genes were also informatically queried for potential gene–drug interactions, yielding a list of 41 drugs including a known SLE therapy. The DM-DE genes delineate two important biologic pathways that are not only reflective of the heterogeneity of SLE but may also correlate with distinct IFN responses that depend on the source, type, and location of nucleic acid molecules and the activated receptors in individual patients. Cell- and tissue-specific analyses will be critical to the understanding of genetic factors dysregulating the nucleic acid-sensing and IFN pathways and whether these factors could be appropriate targets for therapeutic intervention.

Sporadic Pseudohypoparathyroidism Type 1B in Monozygotic Twins: Insights Into the Pathogenesis of Methylation Defects

ContextSporadic pseudohypoparathyroidism type 1B (sporPHP1B) is an imprinting disease without a defined genetic cause, characterized by broad methylation changes in differentially methylated regions (DMRs) of the GNAS gene.ObjectiveThis work aims to provide insights into the causative event leading to the GNAS methylation defects through comprehensive molecular genetic analyses of a pair of female monozygotic twins concordant for sporPHP1B who were conceived naturally, that is, without assisted reproductive techniques.MethodsUsing the leukocyte genome of the twins and family members, we performed targeted bisulfite sequencing, methylation-sensitive restriction enzyme (MSRE)-quantitative polymerase chain reaction (qPCR), whole-genome sequencing (WGS), high-density single-nucleotide polymorphism (SNP) array, and Sanger sequencing.ResultsMethylation analyses by targeted bisulfite sequencing and MSRE-qPCR revealed almost complete losses of methylation at the GNAS AS, XL, and A/B DMRs and a gain of methylation at the NESP55 DMR in the twins, but not in other family members. Except for the GNAS locus, we did not find apparent methylation defects at other imprinted genome loci of the twins. WGS, SNP array, and Sanger sequencing did not detect the previously described genetic defects associated with familial PHP1B. Sanger sequencing also ruled out any novel genetic alterations in the entire NESP55/AS region. However, the analysis of 28 consecutive SNPs could not exclude the possibility of paternal heterodisomy in a span of 22 kb comprising exon NESP55 and AS exon 5.ConclusionOur comprehensive analysis of a pair of monozygotic twins with sporPHP1B ruled out all previously described genetic causes. Twin concordance indicates that the causative event was an imprinting error earlier than the timing of monozygotic twinning.

A novel ARX loss of function variant in female monozygotic twins is associated with chorea

Pathogenic variants in ARX lead to a variety of phenotypes with intellectual disability being a uniform feature. Other features can include severe epilepsy, spasticity, movement disorders, agenesis of the corpus callosum, lissencephaly, hydranencephaly and ambiguous genitalia in males. We present the first report of monozygotic female twins with a de novo ARX pathogenic variant (c.1406_1415del; p. Ala469Aspfs*20), predicted to result in a truncated ARX protein missing the important regulatory Aristaless domain. The twins presented with profound developmental delay and seizures, consistent with the known genotype-phenotype correlation. Twin 2's features were significantly more severe. She also developed chorea; the first time this movement disorder has been seen in an ARX variant other than an expansion of the first polyalanine tract. Differential X-chromosome inactivation was the most likely explanation for the differing severities but could not be conclusively proven.

Twins Separated at Birth: Across a Country and Around the World/Twin Research: Memorial Tribute to Isaac Blickstein, MD; Infanticide and Sacrifice of Archaic-Aged Twins and Triplets; Prehistoric Twin Burials; Highlights from a Conference on Three Identical Strangers/Media Reports: An Atypical Twin Father; An Actor's Twin Brother; Twin Link to Tulsa, Oklahoma Massacre; Superfetated Twins; Twin Comedians and Script Writers; Indian

Every reared-apart monozygotic (MZ) twin pair offers a fresh perspective on human developmental questions. This is true regardless of whether the co-twins were raised in the same country or across the globe. The members of two pairs of separated MZ female twins have recently come to attention. In one case the twins were raised by different families in Argentina; in the other case the twins were raised by different families in Sweden and Vietnam. The perceptions and perspectives of these twins are insightful. The twin research section that follows begins with a tribute to our late esteemed colleague, Dr Isaac Blickstein (1953-2020). Research concerning the infanticide and sacrifice of Archaic-aged twins and triplets and prehistoric twin burials is reviewed next. Highlights from a conference focused on the 2018 film Three Identical Strangers are also included in this portion. The final section of this article includes media reports of an atypical twin father, an actor's twin brother, a twin link to the 1921 Tulsa, Oklahoma massacre, the birth of superfetated twins, twin comedians and script writers and Indian twins' tragic loss to COVID-19.

Twins Are Always Serving Science, What About Their Own Needs? Twins’ Need for Social Anxiety Program

Objective: The effectiveness of the Social Anxiety Program on Adolescent Twins investigated in this study. Method: The study is a mixed-method study using a one-group pretest-posttest design, together with the qualitative method. First, Intraclass Correlation Coefficient used to find out the concordance and differentiation level of the twins&amp;rsquo; social anxiety. Because monozygotic twins&amp;rsquo; concordance rate is higher than dizygotic twins, four pair female monozygotic twins aged 17-18 participated in the group. Wilcoxon Single Ranks Test used to analyze the experimental part of the research. Three sessions of focus groups held after the program. Content analysis techniques used as a qualitative analysis. Result: As a result, there was a statistically significant difference between pre/post-program. Since this difference was in favor of initial measurement, the program interpreted as being effective. Themes also supported the quantitative results. Conclusion: Findings obtained from both experimental and qualitative parts discussed. Suggestions provided for future researcher.

Male microchimerism in females: a quantitative study of twin pedigrees to investigate mechanisms.

STUDY QUESTIONDoes having a male co-twin, older brothers, or sons lead to an increased probability of persistent male microchimerism in female members of twin pedigrees?SUMMARY ANSWERThe presence of a male co-twin did not increase risk of male microchimerism and the prevalence of male microchimerism was not explained by having male offspring or by having an older brother.WHAT IS KNOWN ALREADYMicrochimerism describes the presence of cells within an organism that originate from another zygote and is commonly described as resulting from pregnancy in placental mammals. It is associated with diseases with a female predilection including autoimmune diseases and pregnancy-related complications. However, microchimerism also occurs in nulliparous women; signifying gaps in the understanding of risk factors contributing to persistent microchimerism and the origin of the minor cell population.STUDY DESIGN, SIZE, DURATIONThis cross-sectional study composed of 446 adult female participants of the Netherlands Twin Register (NTR).PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants included in the study were female monozygotic (MZ) twins, female dizygotic same-sex twins and females of dizygotic opposite-sex twin pairs, along with the mothers and sisters of these twins. Peripheral blood samples collected from adult female participants underwent DNA extraction and were biobanked prior to the study. To detect the presence of male-origin microchimerism, DNA samples were tested for the relative quantity of male specific Y chromosome gene DYS14 compared to a common β-globin gene using a highly sensitive quantitative PCR assay.MAIN RESULTS AND THE ROLE OF CHANCEWe observed a large number of women (26.9%) having detectable male microchimerism in their peripheral blood samples. The presence of a male co-twin did not increase risk of male microchimerism (odds ratio (OR) = 1.23: SE 0.40, P = 0.61) and the prevalence of male microchimerism was not explained by having male offspring (OR 0.90: SE 0.19, P = 0.63) or by having an older brother (OR = 1.46: SE 0.32, P = 0.09). The resemblance (correlation) for the presence of microchimerism was similar (P = 0.66) in MZ pairs (0.27; SE 0.37) and in first-degree relatives (0.091; SE 0.092). However, age had a positive relationship with the presence of male microchimerism (P = 0.02).LIMITATIONS, REASONS FOR CAUTIONAfter stratifying for variables of interest, some participant groups resulted in a low numbers of subjects. We investigated microchimerism in peripheral blood due to the proposed mechanism of cell acquisition via transplacental blood exchange; however, this does not represent global chimerism in the individual and microchimerism may localize to numerous other tissues.WIDER IMPLICATIONS OF THE FINDINGSImmune regulation during pregnancy is known to mitigate allosensitization and support tolerance to non-inherited antigens found on donor cells. While unable to identify a specific source that promotes microchimerism prevalence within pedigrees, this study points to the underlying complexities of natural microchimerism in the general population. These findings support previous studies which have identified the presence of male microchimerism among women with no history of pregnancy, suggesting alternative sources of microchimerism. The association of detectable male microchimerism with age is suggestive of additional factors including time, molecular characteristics and environment playing a critical role in the prevalence of persistent microchimerism. The present study necessitates investigation into the molecular underpinnings of natural chimerism to provide insight into women’s health, transplant medicine and immunology.STUDY FUNDING/COMPETING INTEREST(S)This work is funded by Royal Netherlands Academy of Science Professor Award (PAH/6635 to D.I.B.); The Netherlands Organisation for Health Research and Development (ZonMw)—Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw 911-09-032); Biobanking and Biomolecular Research Infrastructure (BBMRI–NL, 184.021.007; 184.033.111); The Netherlands Organisation for Scientific Research (NWO)—Netherlands Twin Registry Repository (NWO-Groot 480-15-001/674); the National Institutes of Health—The Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06), Grand Opportunity grants Integration of genomics and transcriptomics in normal twins and major depression (NIMH 1RC2 MH089951-01), and Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); and European Research Council—Genetics of Mental Illness (ERC 230374). C.B.L. declares a competing interest as editor-in-chief of Human Reproduction and his department receives unrestricted research grants from Ferring, Merck and Guerbet. All remaining authors have no conflict-of-interest to declare in regards to this work.TRIAL REGISTRATION NUMBERN/A.