Reversal of Autism Symptoms among Dizygotic Twins through a Personalized Lifestyle and Environmental Modification Approach: A Case Report and Review of the Literature.

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990's, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating the reversal of autism diagnoses, with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism symptoms among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD "requiring very substantial support" at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin's symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins' symptoms, which manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing modifiable environmental and lifestyle risk factors.

Whole-genome sequences reveal zygotic composition in chimeric twins.

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.

Maternal and perinatal risks for monozygotic twins conceived following frozen-thawed embryo transfer: a retrospective cohort study.

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.

Environment-by-PGS Interaction in the Classical Twin Design: An Application to Childhood Anxiety and Negative Affect.

One type of genotype-environment interaction occurs when genetic effects on a phenotype are moderated by an environment; or when environmental effects on a phenotype are moderated by genes. Here we outline these types of genotype-environment interaction models, and propose a test of genotype-environment interaction based on the classical twin design, which includes observed genetic variables (polygenic scores: PGSs) that account for part of the genetic variance of the phenotype. We introduce environment-by-PGS interaction and the results of a simulation study to address statistical power and parameter recovery. Next, we apply the model to empirical data on anxiety and negative affect in children. The power to detect environment-by-PGS interaction depends on the heritability of the phenotype, and the strength of the PGS. The simulation results indicate that under realistic conditions of sample size, heritability and strength of the interaction, the environment-by-PGS model is a viable approach to detect genotype-environment interaction. In 7-year-old children, we defined two PGS based on the largest genetic association studies for 2 traits that are genetically correlated to childhood anxiety and negative affect, namely major depression (MDD) and intelligence (IQ). We find that common environmental influences on negative affect are amplified for children with a lower IQ-PGS.

Comparison of the Concordance of Allergic Diseases between Monozygotic and Dizygotic Twins: A Cross-Sectional Study Using KoGES HTS Data.

Several epidemiological studies have demonstrated that genetic and environmental factors contribute to the development of allergic diseases. However, there is limited information on these factors in the Korean population. This study investigated the importance of genetic and environmental factors in allergic diseases, such as allergic rhinitis, asthma, allergic conjunctivitis, or atopic dermatitis, by comparing the disease incidence in Korean adult monozygotic and dizygotic twins. This cross-sectional study utilized data from 1296 twin pairs, including 1052 monozygotic and 244 dizygotic twins, aged over 20 years, from the Korean Genome and Epidemiology Study (2005-2014). The study utilized binomial and multinomial logistic regression models to compute odds ratios of disease concordance. The concordance rate (92%) of the presence or absence of atopic dermatitis in monozygotic twins was slightly higher than that in dizygotic twins (90.2%), which only had a borderline significance (p = 0.090). The concordance rates of other allergic diseases within monozygotic twins were lower compared to dizygotic twins (asthma, 94.3% vs. 95.1%; allergic rhinitis, 77.5% vs. 78.7%; allergic conjunctivitis, 90.6% vs. 91.8%), of which the differences were not statistically significant. Monozygotic twins had a higher proportion of cases in which both siblings had allergic diseases than dizygotic twins (asthma, 1.1% vs. 0.0%; allergic rhinitis, 6.7% vs. 3.3%; atopic dermatitis, 2.9% vs. 0.0%; allergic conjunctivitis, 1.5% vs. 0.0%), of which the differences were also not statistically significant. In conclusion, our results appear to indicate the relative importance of environmental factors over genetic factor in the development of allergic diseases in Korean adult monozygotic twins.

Twins' Macular Pigment Optical Density Assessment and Relation with SCARB1 Gene Polymorphism.

THE AIM OF THE STUDY: to assess the influence of genetic and environmental factors using twin studies and evaluate the associations of SCARB1 gene variants (rs11057841) with AMD and MPOD. MATERIAL AND METHODS: a total of 108 healthy twins (56 MZ and 52 DZ twins) were tested in this study. The MPOD was measured using the one-wavelength reflectometry method. Fundus reflectance (Visucam 500, reflectance of a single 460 nm wavelength) was used to measure the MPOD levels, MPOD parameters including max and mean optical density (OD), and area and volume. Real-time polymerase chain reaction was used to detect single nucleotide polymorphisms. RESULTS: we detected a positive correlation of MPOD in the right and left eyes in MZ twin pairs (r = 0.830 and r = 0.860, respectively) (p < 0.0001) and a negative correlation of MPOD in the right and left eyes in DZ twin pairs (r = 0.314 and r = 0.408, respectively) (p < 0.05). The study was able to identify statistically significant differences in mean MPOD values in the right and left eyes between subjects with a wild-type CC genotype and a CT genotype with a risk allele. A decrease in the mean MPOD value was observed in group II with a CT genotype (0.110 d.u.) compared with the CC genotype (0.117 d.u.) in the right eye (p = 0.037) and in the left eye with a CT genotype (0.109 d.u.) compared with a CC genotype in the subjects (0.114 d.u.) (p = 0.038). In the right eye, in group II (0.101-0.128 d.u.), those with a CT genotype (n = 6) with one risk allele had a statistically significantly lower (0.110 d.u.) mean average MPOD value compared with those with a wild-type CC genotype (n = 25) (0.117 d.u.) (p = 0.037). CONCLUSION: this twin study showed a strong heritability of the retina pigment, which was 86% prevalent in Lithuania. Individuals with a CT genotype of the SCARB1 rs11057841 with a risk allele had statistically significantly lower mean MPOD values in both eyes compared to subjects with a wild-type CC genotype.

Different Clinical Courses of Nephronophthisis in Dizygotic Twins.

Siblings with nephronophthisis occasionally show different clinical courses; however, the reasons for this remain unclear. We herein report cases of nephronophthisis in a pair of dizygotic twins with different clinical courses. The brother developed end-stage kidney disease at 17 years old; however, his sister did not show kidney insufficiency. Kidney biopsies revealed severe tubulointerstitial damage at 14 and 22 years old in the brother and sister, respectively. Both had a homozygous NPHP1 deletion with different heterozygous mutations related to hereditary cystic kidney disease. Since the dizygotic twins were exposed to similar environmental factors, genetic factors may have influenced their clinical course more strongly than environmental factors.

Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data.

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005−2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.

Comparison of Concordance of Peptic Ulcer Disease, Non-Adenomatous Intestinal Polyp, and Gallstone Disease in Korean Monozygotic and Dizygotic Twins: A Cross-Sectional Study.

Epidemiological studies have suggested the role of multiple genetic and environmental factors in the development of non-neoplastic gastrointestinal (GI) diseases; however, little information is available on these factors in the Korean population. Therefore, this cross-sectional study explored the effect of these factors by analyzing the concordance of several benign GI disorders in 525 monozygotic twins compared to that in 122 dizygotic twins aged >20 years from the Healthy Twin Study data of the Korean Genome and Epidemiology Study (2005-2014). Chi-square test, Wilcoxon rank-sum, and binomial and multinomial logistic regression models were used for statistical analysis. There was lack of concordance of gastric/duodenal ulcers and cholelithiasis/cholangitis between monozygotic twins compared to that in dizygotic twins, suggesting that environmental factors may mediate those concordant disease expressions in monozygotic twins. The concordance of intestinal polyps in monozygotic twins was 32% lower than that in dizygotic twins (p = 0.028), indicating that the effect of genetic factors on the risk for intestinal polyp development may be low. In conclusion, the lack or low concordance of several benign GI diseases between monozygotic and dizygotic twin groups suggests the relative importance of environmental factors, indicating that these are preventable diseases.

Physical growth and intelligence development of discordant dizygotic twins from birth to preschool age: a prospective cohort study.

BACKGROUND: The majority of studies are limited to adverse perinatal outcomes and poor cognitive abilities in the short term in discordant monochorionic twins. METHODS: To determine whether small and large discordant dizygotic twins differ in physical growth and intelligence development and weight and height from birth up to 6 years of age were measured in 34 dizygotic twin pairs with ≥ 20% birth weight discordance. Mental developmental index (MDI) and psychomotor developmental index (PDI) were calculated at 1 year, while the Wechsler Intelligence Scale for Children-IV (WISC-IV) full-scale intelligence quotient (IQ) was assessed at the age of 6. RESULTS: The difference in height and weight in each stage differed significantly from birth to 72-months-old (P < 0.05), although there was disappointing catch-up growth in smaller twins. PDI but not MDI at 1 year of age was significantly different between the two groups (P < 0.05), and smaller twins experienced higher psychomotor retardation rates (P < 0.05). Also, the influence of height and weight on PDI was statistically significant (P < 0.05). No significant difference was detected in the WISC-IV full-scale IQ at the age of 6; however, the full-scale IQ may be affected by the history of suffocation and the S/D value (P = 0.011, P = 0.022). CONCLUSIONS: Intrauterine fetal growth and development lead to birth weight differences in twins and sustain an impact on the children's physical growth in height and weight from birth to preschool age, causing psychomotor developmental differences at 1 year of age. However, the differences in psychomotor development decrease gradually by the age of 6.

Comparison of the Coincidence of Osteoporosis, Fracture, Arthritis Histories, and DEXA T-Score between Monozygotic and Dizygotic Twins: A Cross-Sectional Study Using KoGES HTS Data.

We explored the genetic and environmental inter-relationships among osteoporosis, fracture, arthritis, and bone mineral density concordance in monozygotic twins compared to those in dizygotic twins. This cross-sectional research assessed data of 1032 monozygotic and 242 dizygotic twin pairs aged >20 years included in the Healthy Twin Study data of the Korean Genome and Epidemiology Study between 2005 and 2014. Outcomes of interest included illness concordance and absolute differences in dual-energy X-ray absorptiometry (DEXA) T-scores. We found comparable concordances of osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis between monozygotic and dizygotic twins. Medical histories of osteoporosis, fractures caused by accident or falling, osteoarthritis, and rheumatoid arthritis were not distinct between monozygotic and dizygotic twins. Accidental fracture occurrence in both monozygotic twins showed significantly lower odds than that in dizygotic twins. Genetic influence on liability to fracture risk might thus be maintained. DEXA T-scores for bone mineral density indicated more comparable tendencies within monozygotic twin pairs than within dizygotic ones, suggesting the relative importance of genetic contribution to bone mineral density. The relative importance of genetic factors in bone mineral density is sustained between monozygotic twins; overt disease expression of osteoporosis, fractures, or arthritis may be affected by environmental factors.

Rare spontaneous monochorionic dizygotic twins: a case report and a systematic review.

BACKGROUND: Monochorionic dizygotic twins are a rare condition, mostly related to assisted reproductive technology. This type of twinning is burdened by the same risk of pregnancy complications found in monochorionic monozygotic pregnancies. CASE PRESENTATION: We report a case of spontaneous monochorionic dizygotic twins sharing situs inversus abdominalis and isolated levocardia, with only one twin affected by biliary atresia with splenic malformation syndrome. We also conducted a literature review of the 14 available documented monochorionic dizygotic twin gestations spontaneously conceived. CONCLUSIONS: It is still unclear how this unusual type of twinning can occur in spontaneous conception. The evidence so far suggest the importance to timely diagnose the chorionicity, in order to adequately manage the typical complications associated with monochorionicity.

Novel IL2RG Gene Mutation in One of Dizygotic Twins Causing Profound Changes of Receptor Structure.

In this study, we report a 4-month-old boy with T-B+NK- severe combined immunodeficiency (SCID) due to a novel mutation in exon 2 of IL2RG, the gene encoding the interleukin (IL) common gamma chain (γc) of the cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The patient was born from a twin pregnancy. He manifested recurrent infections of the gastrointestinal tract, whereas his twin brother was asymptomatic with no immune defects. In order to evaluate the effect of this unreported variant on the protein structure, a structural modeling process was performed showing prominent biochemical alterations of the protein features, including molecular weight, isoelectric charge, and possible changes to its secondary and tertiary structure.

The Heritability of Twinning in Seven Large Historic Pedigrees.

It is widely recognized that dizygotic twinning (DZT) runs in families, but estimates of heritability from twin and family data are remarkably scarce and vary considerably. Here, we traced seven large, sometimes historical, multigeneration pedigrees from West Africans, fin de siècle French Jews, Canadians (two pedigrees), and the French royal family, in which twin births were recorded. We estimated heritability of twinning (of all types) as zygosity information was not available, diluting the true DZT heritability by a third or so. The estimates in the range 8-20% are remarkably consistent across time (8-19 generations) and ethnicities and also consistent with twin and family estimates.

Generation and characterization of human-derived iPSC lines from one pair of dizygotic twins discordant for schizophrenia.

Schizophrenia (SCZ) is a debilitating neurodevelopmental disorder with a high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by a pair of dizygotic twins. The female was clinically diagnosed as SCZ by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria, and her unaffected male sibling was healthy control. Induced pluripotent stem cells (iPSCs) were established using Episomal vectors carrying reprograming factors OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT. These lines with normal karyotype highly expressed pluripotency markers and are capable to differentiate into derivatives of three germ layers. Both lines are negative of mycoplasma.

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

STUDY QUESTION: Does 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 ANSWER: The 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 ALREADY: Microchimerism 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, DURATION: This cross-sectional study composed of 446 adult female participants of the Netherlands Twin Register (NTR). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants 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 ß-globin gene using a highly sensitive quantitative PCR assay. MAIN RESULTS AND THE ROLE OF CHANCE: We 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 CAUTION: After 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 FINDINGS: Immune 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 NUMBER: N/A.

Three dimensional gait analyses in dizygotic twin athletes.

Gait analysis and gait indices are frequently used to evaluate gait pathologies and outcomes. The aim of this study is to investigate the differences in gait parameters of dizygotic twin athletes according to each other and athletes group who are similar age but non-twin. Eighty-four athletes without any disease that could cause gait pathology were included the study. Time-distance measurements, kinematic - kinetic variables, and gait deviation index (GDI) of the gait functions of twin athletes (17 boys and 25 girls, height: 153.9 ± 15 cm, weight: 45.9 ± 12 kg, leg length 80.5 ± 11 cm) were compared with each other and with 42 sex and age matched non-twins athletes (height: 155 ± 15 cm, weight: 47 ± 14 kg, leg length 80.6 ± 9.8 cm, mean age 11.8 ± 2.29, range 6-15 years). No statistically significant difference was found about the time, distance parameters and GDIs in comparison of twin athletes with each other and the non-twin group. Additionally, kinetic and kinematic variables were similar in between twins. We measured lower adduction angles and higher abduction angles in non-twin athletes in comparison to the twin athletes (p = 0.01, 0.04). Additionally, the angle of knee flexion at the first contact was higher in non-twins (p = 0.003).Being dizygotic twin seems to have no clinical effect on gait function in athletes.

Novel BEST1 mutation in autosomal recessive bestrophinopathy in Japanese siblings.

PURPOSE: Autosomal recessive bestrophinopathy (ARB) is a disease that results from the mutations in the BEST1 gene. It is characterized by multifocal yellowish lipofuscin deposits, cystoid macular edema, and subretinal fluid. Among approximately 270 BEST1 mutations, only 40 that include both heterozygous and homozygous mutations are associated with ARB. However, very few ARB-related mutations have been reported in the Japanese population. Therefore, in this study, we aimed to identify BEST1 mutations and describe the genotype-phenotype relationship in Japanese dizygotic twins presenting with ARB. MATERIALS AND METHODS: We performed clinical examinations in Japanese dizygotic twin patients (male: 29 years) with ARB as well as whole-exome sequencing in seven family members of these twins. RESULTS: In this study, we have reported on a novel BEST1 mutation, the p. Phe151Cys mutation, associated with ARB in Japanese dizygotic twins who had bi-allelic p. Ala160Pro mutations in BEST1. The clinical features observed were binocular abnormalities of the fundus, such as multifocal yellowish subretinal deposits, cystoid macular edema, and subretinal fluid. The full-field electroretinography results were subnormal. CONCLUSION: It was indicated that the novel BEST1 mutations identified may be strongly correlated with binocular ARB. This study provides significant information of the genotype-phenotype association in Japanese ARB patients. Further, the genetic analysis that we performed was very useful for the differential diagnosis and might have implications in the development of future treatment modalities.

Human Connectome Project: heritability of brain volumes in young healthy adults.

Here we report on the heritability and Intraclass Correlation Coefficients (ICCs) of brain volumes in 1,103 young healthy adults with mean age 29.2 years. Among them are: 153 monozygotic (MZ) twin pairs and 86 dizygotic (DZ) twin pairs, 133 non-twin siblings of MZ twins, 76 non-twin siblings of DZ twins, 335 siblings, and 81 unrelated individuals. ICCs were calculated between pairs of the following genetic groups: (1) MZ twins; (2) DZ twins; (3) MZ twins-their singleton siblings; (4) DZ twins-their singleton siblings; (5) siblings (SB); and (6) unrelated individuals (NR). We studied 4 brain groups: global, lobar, subcortical, and cortical brain regions. For each of 4 brain groups we found the same order of ICCs ranging from the highest values for MZ twins, statistically significantly smaller for the DZ twins and 3 sibling groups, and practically zero for NR. The DZ twins and 3 sibling groups were not different. No hemispheric difference was found in any genetic group. Among brain groups, the highest heritability was for the global regions, followed by lobar and subcortical groups. Only the cortical brain group heritability was statistically lower than other brain groups. We found less genetic control on the left hemisphere than on the right but no significant difference between hemispheres, and no hemispheric lateralization of heritability for any of the brain groups. These findings document substantial and systematic heritability of global and regional brain volumes.

Three Patterns of Inheritance of Quantitative Dermatoglyphic Traits: Kosovo Albanian Twin Study.

Dermatoglyphs are epidermal ridge configurations on the fingers, palms and soles that are formed during fetal development, and therefore only the intrauterine environment can have any influence on their formation. This study aims at investigating the genetic and environmental contribution in determining quantitative dermatoglyphic traits in 32 monozygotic (MZ) and 35 dizygotic (DZ) same-sex twins from the Albanian population of Kosovo. All genetic analyses were run in the statistical program Mx. After assumptions testing, based on the pattern of MZ-DZ correlations, univariate models were fitted to the data in order to estimate additive genetic (A), common (C) and individual (E) environmental influences for all variables. The exception was the atd-angle for which a model with nonadditive genetic (D) influences was tested, since DZ correlations were less than half of MZ correlations. Goodness of fit of the full ACE or ADE model was compared to the saturated model. The fit of nested models (AE, CE, DE or E) was compared to the full models (ACE or ADE). Our results indicate that additive genetic component strongly contributes to individual differences in finger ridge counts (49-81%), and weakly (0-50%) on the formation of the palmar ridge counts between the palmar triradii a, b, c, and d. The specific pattern found for the atd-angle implies the impact of a nonadditive genetic component, possibly the effect of a major gene. Further, more powered studies are needed to confirm this pattern, especially for resolving the issue of the huge difference in MZ and DZ twin similarity for the atd-angle palmar trait.