Impact of GSTT1 AND GSTM1 variants and hair mercury concentration in maternal blood pressure among coastal pregnant women in Central Java, Indonesia.

The GSTT1 and GSTM1 genes have a role in mercury metabolism and excretion, as well as blood pressure response, impacting birth outcomes. The present study assesses whether GSTT1 and GSTM1 deletion variants and maternal hair Hg concentration are associated with blood pressure and birth outcomes among the Indonesian coastal pregnant mother population. A cross-sectional study was conducted on 139 pregnant women in the Jepara coastal area of Central Java, Indonesia. Maternal characteristics during pregnancy, including blood pressure and birth outcomes, were collected. GSTT1 and GSTM1 gene variants were detected using polymerase chain reaction (PCR). Hair Hg levels were measured using the reducing-vaporization mercury analyzer. The mean maternal hair Hg concentration was 0.727±0.558 µg/g. GSTT1 genotype homozygous deletion was found in 41.7% of subjects, while no GSTM1 deletion was found. No statistically significant difference was found between deletion and non-deletion groups for hair Hg. GSTT1 deletion genotype shows protection but is inconclusive toward diastolic hypertension (p=0.048, OR 0.285, CI 0.077-1.052) and insignificant with birth outcomes (all p>0.05). High hair Hg concentration and positive history of cardiovascular diseases increase the risk of systolic and diastolic hypertension during pregnancy with OR 6.871 (CI 95% 1.445-32.660) and 8.518 (CI 95% 2.126-34.125), respectively, while not in birth outcomes. Maternal Hg exposure and history of cardiovascular diseases are independent risk factors for pregnant hypertension, whereas the GSTT1 homozygous deletion genotype has no role in diastolic hypertension and birth outcomes among the Indonesian coastal pregnant mother population.

Comparing the risk factors of nephrolithiasis in Asian countries population: A systematic review and meta-analysis.

This systematic review and meta-analysis aims to identify the main risk factors for nephrolithiasis in Asian populations, with comparisons to European and American populations. Using a comprehensive literature search across PubMed, Science Direct, and ResearchGate, in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines, we synthesized data from 11 geographically diverse studies. Our findings reveal substantial population-specific differences in nephrolithiasis risk factors, particularly familial history, water consumption, and smoking patterns. In Asian populations, a 60% increase in risk was associated with a family history of nephrolithiasis. In the meantime, drinking sources also affected nephrolithiasis risk, with the consumption of boiled water being associated with a 25% increase in risk compared to consumption of bottled or mineral water. These findings highlight the importance of tailoring preventive strategies and treatments to specific risk factors, taking into account regional variations, and call for additional research to understand the complex interaction between genetic, environmental, and lifestyle factors in the development of nephrolithiasis.

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

The Role of Body Mass Index, Advanced Age, and Low Educational Attainment in Mild Cognitive Impairment among the Older Adult Population: A Study in a Rural Area in Indonesia.

This study evaluated the prevalence of mild cognitive impairment (MCI) and factors associated with MCI among older adults in a rural area of Indonesia. This cross-sectional study was conducted in a rural area of East Java, Indonesia. Four hundred and twenty-seven older adults aged ≥60 years were included in the study. MCI was assessed using the Brain Health Test Cognitive Tool. Data related to possible risk factors were obtained using semi-structured questionnaires. The indirect body mass index was determined based on ulnar length. The prevalence of MCI was 12.9%. Being underweight (<18.5 kg/m2) (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.17-4.97; p = 0.016), requiring assistance to manage money or medications (OR, 2.72; 95% CI, 1.02-7.23; p = 0.045), age ≥70 years (OR, 2.50; 95% CI, 1.11-5.60; p = 0.026), and having an educational attainment of ≤6 years (OR, 4.92; 95% CI, 1.92-12.60; p = 0.001) were significantly associated with MCI. In this Indonesian older adult population, underweight people who had an educational attainment of <6 years, those aged ≥70 years, and those who needed assistance to manage money or medications were more likely to have MCI.

Factors influencing illness uncertainty in parents of children with congenital adrenal hyperplasia in a developing country: A cross-sectional study.

Background: Illness uncertainty in parents of children with congenital adrenal hyperplasia (CAH) refers to parents' inability to create meaning in events related to their children having CAH. This may influence their role in caring for children with CAH. Objective: The study aimed to determine factors associated with illness uncertainty experienced by parents of children with CAH in a developing country. Methods: A cross-sectional study was conducted on 80 parents (43 mothers and 37 fathers) of children with CAH, selected using consecutive sampling methods. The Parent's Perception of Uncertainty Scale (PPUS) was used to measure the illness uncertainty levels. Data were collected from March 2020 to October 2020. Independent t-test and chi-square test were used to determine factors (parent's gender, age, educational level, monthly household income, number of children with CAH, history of child death due to CAH, child's age when first diagnosed with CAH, duration of therapy, gender change, type of CAH (salt wasting/SW or simple virilizing/SV), current gender, and genitoplasty) influencing illness uncertainty in parents. Results: The mean scores of PPUS were 42.3 ± 12.91, and the majority of parents had a low PPUS score (49; 61%). Parents of children with SW-CAH showed higher uncertainty (44.2 ± 12.77) than those with SV-CAH (32.6 ± 8.86; p = 0.003). Parents who lost their children due to CAH were more likely to report a moderate illness uncertainty than parents who never experienced child mortality due to CAH (χ2(1, 80) = 4.893; p = 0.027). Conclusion: The factors significantly affecting uncertainty in parents of children with CAH determined in this study might help healthcare professionals, including nurses, to play a pivotal role in giving pertinent information regarding their children's health, disease, and therapy to help manage parental uncertainty.

Genetic diagnostic approach to intellectual disability and multiple congenital anomalies in Indonesia.

Intellectual disability (ID) and multiple congenital anomalies (MCA) are major contributors to infant mortality, childhood morbidity, and long-term disability, with multifactorial aetiology including genetics. We aim to set a diagnostic approach for genetic evaluation of patients with ID and MCA, which can be applied efficiently with a good diagnostic rate in Indonesia or other low resources settings. Out of 131 ID cases, twenty-three individuals with ID/global developmental delay (GDD) and MCA were selected from two-steps of dysmorphology screening and evaluation. Genetic analysis included chromosomal microarray (CMA) analysis, targeted panel gene sequencing, and exome sequencing (ES). CMA revealed conclusive results for seven individuals. Meanwhile, two out of four cases were diagnosed by targeted gene sequencing. Five out of seven individuals were diagnosed using ES testing. Based on the experience, a novel and comprehensive flowchart combining thorough physical and dysmorphology evaluation, followed by suitable genetic tests is proposed as a diagnostic approach to elucidate the genetic factor(s) of ID/GDD and MCA in low resources settings such as Indonesia.

The effectiveness of atorvastatin for the prevention of deep vein thrombosis in cancer patients undergoing chemotherapy : A randomised controlled trial: open label.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication in cancer. Although thromboprophylaxis in cancer patients is recommended by the guidelines, clinicians' use of thromboprophylaxis remains limited due to cost, bleeding complications, and reluctance to give injectable anticoagulants. Inflammation plays essential roles in the pathogenesis of cancer-associated thrombosis. Owing to its ability to decrease proinflammatory cytokines, statins have anti-inflammatory properties. Thus, statins can be possibly utilized as thromboprophylaxis therapy in cancer patients undergoing chemotherapy. OBJECTIVE: To compare the effectiveness of atorvastatin and rivaroxaban for DVT prevention in high-risk thrombosis patients with cancer undergoing chemotherapy. METHODS: Double-blind, randomized controlled trial involving cancer patients with high-risk of thrombosis undergoing chemotherapy. We randomly assigned patients without deep-vein thrombosis at screening to receive atorvastatin 20 mg or rivaroxaban 10 mg daily for up to 90 days. Doppler ultrasonography was performed 90 days following chemotherapy to diagnose DVT. Average cost-effectiveness analysis was performed to analyze the cost of atorvastatin compared to rivaroxaban. RESULTS: Of the eighty six patients who underwent randomization, primary efficacy end point was observed in 1 of 42 patients (2.3%) in the atorvastatin group and in 1 of 44 (2.2%) in the rivaroxaban group (Odds Ratio [OR], 0.953; 95% confidence interval [CI], 0.240 to 3.971; p = 1.000). There was a significant difference in the incidence of major bleeding, 2 of 42 patients (4.8%) in the atorvastatin group and 12 of 44 (27.3%) in the rivaroxaban group (OR, 0.257; 95% CI, 0.07 to 0.94; p = 0.007). The average cost-effectiveness ratio of using atorvastatin was lower than that of rivaroxaban. CONCLUSION: Atorvastatin did not differ significantly from rivaroxaban in reducing the incidence of DVT, lower bleeding risk, and cost-effectiveness for thromboprophylaxis in high-risk thrombosis patients with cancer undergoing chemotherapy. The presence of limited statistical power and wide confidence intervals in this study needs further study to strengthen the efficacy of atorvastatin as DVT prophylaxis in cancer patients. TRIAL REGISTRATION: ISRCTN71891829, Registration Date: 17/12/2020.

Analysis of contact pressure in a 3D model of dual-mobility hip joint prosthesis under a gait cycle.

Hip joint prostheses are used to replace hip joint function in the human body. The latest dual-mobility hip joint prosthesis has an additional component of an outer liner that acts as a cover for the liner component. Research on the contact pressure generated on the latest model of a dual-mobility hip joint prosthesis under a gait cycle has never been done before. The model is made of ultrahigh molecular weight polyethylene (UHMWPE) on the inner liner and 316L stainless steel (SS 316L) on the outer liner and acetabular cup. Simulation modeling using the finite element method is considered static loading with an implicit solver for studying the geometric parameter design of dual-mobility hip joint prostheses. In this study, simulation modeling was carried out by applying varying inclination angles of 30°, 40°, 45°, 50°, 60°, and 70° to the acetabular cup component. Three-dimensional loads were placed on femoral head reference points with variations of femoral head diameter used at 22 mm, 28 mm, and 32 mm. The results in the inner surface of the inner liner, the outer surface of the outer liner, and the inner surface of the acetabular cup showed that the variations in inclination angle do not have a major effect on the maximum contact pressure value on the liner component, where the acetabular cup with an inclination angle of 45° can reduce contact pressure more than the other studied inclination angle variations. In addition, it was found that the 22 mm diameter of the femoral head increases the contact pressure. The use of a larger diameter femoral head with an acetabular cup configuration at a 45° inclination can minimize the risk of implant failure due to wear.

The aberrant behavior profile in Indonesian individuals with fragile X syndrome with limited genetic services.

Fragile X syndrome (FXS) is caused by the full mutation in the fragile x messenger ribonucleoprotein 1 (FMR1) gene leading to the absence of the fragile X protein (FXP). Previous studies show that individuals with FXS exhibit changing behavior over time; therefore, this study aimed to elucidate the aberrant behavior profile of FXS individuals. The Aberrant Behavior Checklist-Community (ABC-C) was used to measure the aberrant behavior profile of individuals with FXS, which was rated by the parent/caregiver combined with clinical impression. A total of 58 items were used to assess aberrant behaviors across five subscales. Forty-nine individuals with FXS were included (32 males, 17 females) with a mean age of 32.9 ± 14.62 years in males and 33.4 ± 13.98 years in females. The average score of irritability and hyperactivity was significantly higher in male FXS individuals (5.37 ± 6.231 and 10.28 ± 8.524) than in female individuals (3.24 ± 7.093 and 3.76 ± 3.327) with p = 0.046 and p = 0.001, respectively. Overall irritability in FXS individuals significantly decreased over time (ß = -0.141; p = 0.032). A modest worsening in lethargy/social withdrawal in males across age and a gentle improvement in hyperactivity/noncompliance in male of FXS individuals were observed. FXS males had higher hyperactivity problems than FXS female individuals across age.

Adopted walking condition for computational simulation approach on bearing of hip joint prosthesis: review over the past 30 years.

Bearing on artificial hip joint experiences friction, wear, and surface damage that impact on overall performance and leading to failure at a particular time due to continuous contact that endangers the user. Assessing bearing hip joint using clinical study, experimental testing, and mathematical formula approach is challenging because there are some obstacles from each approach. Computational simulation is an effective alternative approach that is affordable, relatively fast, and more accessible than other approaches in examining various complex conditions requiring extensive resources and several different parameters. In particular, different gait cycles affect the sliding distance and distribution of gait loading acting on the joints. Appropriate selection and addition of gait cycles in computation modelling are crucial for accurate and reliable prediction and analysis of bearing performance such as wear a failure of implants. However, a wide spread of gait cycles and loading data are being considered and studied by researchers as reported in literature. The current article describes a comprehensive literature review adopted walking condition that has been carried out to study bearing using computational simulation approach over the past 30 years. Many knowledge gaps related to adoption procedures, simplification, and future research have been identified to obtain bearing analysis results with more realistic computational simulation approach according to physiological human hip joints.

A Case-Control Study of the MTHFR C665T Gene Polymorphism on Macrocytic Anemia Among HIV-Infected Patients Receiving Zidovudine.

Background: Macrocytic anemia is the most common anemia in HIV-infected patients receiving zidovudine, and is closely related to folate and vitamin B12 deficiencies. Homocysteine >10 µmol/L and increased MMA (methylmalonic acid) levels >24.8 ng/mL indicate high/low folate and vitamin B12 deficiencies. Furthermore, MTHFR (Methylene-tetrahydrofolate-reductase) plays an essential role in the transmethylation of homocysteine to methionine and is related to DNA synthesis. The MTHFR C665T gene polymorphism decreases the activity of MTHFR, which culminates in homocysteinemia. Therefore, this case-control aims to assess the role of the MTHFR C665T gene polymorphism on the risk of macrocytic anemia among HIV-infected individuals receiving zidovudine. Methods: This study was conducted using an unmatched case-control design and the participants were HIV-infected adults aged 20 to 59 years old, receiving zidovudine for four weeks and above. A sample of 232 patients was divided into case group with macrocytic anemia and the control having no anemia. Multivariate logistic regression analysis was then implemented to determine the risk factors. Results: The results showed that there was a significant difference in the number of female and male patients namely 51.3% and 48.7%, respectively, with p< 0.001. Moreover, the mean age of the cases and control group was 41.9 ± 9.4 and 36.2 ± 8.3. Regarding education, there were significant differences between subjects with low and high education 47.8% vs 52.2% with p<0.001. The majority of patients or 90.95% had taken AZT for more than 6 months. The logistic regression analysis test results showed that sex, age, education level, duration of AZT use, and homocysteine levels were predictors of macrocytic anemia with p<0.05, while MTHFR C665T gene polymorphism and MMA levels were not risk factors. Conclusion: MTHFR C665T gene polymorphism does not contribute to the incidence of macrocytic anemia among HIV-infected individuals receiving zidovudine.

Physiological Effect of Deep Pressure in Reducing Anxiety of Children with ASD during Traveling: A Public Transportation Setting.

Traveling with children with autism can be very challenging for parents due to their reactions to sensory stimuli resulting in behavioral problems, which lead to self-injury and danger for themselves and others. Deep pressure was reported to have a calming effect on people with autism. This study was designed to investigate the physiological effect of deep pressure, which is an autism hug machine portable seat (AHMPS) in children with autism spectrum disorders (ASD) in public transportation settings. The study was conducted with 20 children with ASD (16 boys and 4 girls) at the Semarang Public Special School with an age ranging from 4 to 13 years (mean 10.9 ± 2.26 years), who were randomly assigned into two groups. The experiment consisted of group I who used the AHMPS inflatable wraps model and group II who used the AHMPS manual pull model. Heart rate (HR) and skin conductance (SC) were analyzed to measure the physiological calming effect using pulse oximeter oximetry and a galvanic skin response (GSR) sensor. Heart rate was significantly decreased during the treatment compared to the baseline (pre-test) session in group I (inflating wrap model) with p = 0.019, while no change of heart rate variability (HRV) was found in group II (manual pull model) with p = 0.111. There was no remaining effect of deep pressure using the HRV indicator after the treatment in both groups (group I with p = 0.159 and group II with p = 0.566). GSR captured the significant decrease in skin conductance during the treatment with p < 0.0001 in group I, but no significant decrease was recorded in group II with p = 0.062. A skin conductance indicator captured the remaining effect of deep pressure (after the treatment); it was better in group I (p = 0.003) than in group II (p = 0.773). In conclusion, the deep pressure of the AHMPS inflating wrap decreases physiological arousal in children with ASD during traveling.

Effect of Short-Term Deep-Pressure Portable Seat on Behavioral and Biological Stress in Children with Autism Spectrum Disorders: A Pilot Study.

Children with autism spectrum disorder (ASD) have challenging behaviors, which are associated with difficulties in parenting. Deep pressure is a therapeutic modality in occupational therapy, and it was reported to produce a calming effect. This study aimed to determine whether the short-term use of an autism hug machine portable seat (AHMPS) improves behavioral and neurobiological stress in children with ASD, and to determine whether AHMPS with an inflatable wrap or manual pull is more effective. This study enrolled children with ASD who were administered with the inflatable wrap (group I) and manual pull (group II) for 20 min twice a week for 3 weeks. Conners' Parent Rating Scale-48 (CPRS-48) was used to rate behavioral improvements, and galvanic skin response (GSR) was used to measure sympathetic stress response. A total of 20 children with ASD (14 boys and 6 girls; aged 7-13 years) were included. CPRS-48 presented conduct problems: behavior was significantly decreased in the inflatable group (p = 0.007) compared to the manual pull group. The GSR captured a significant reduction in sympathetic response (p = 0.01) only in group I. Neurobiological stress was reduced in children who were wearing the AHMPS inflatable wrap; therefore, AHMPS inflatable wrap is an effective method to reduce emotional arousal.

Tresca Stress Simulation of Metal-on-Metal Total Hip Arthroplasty during Normal Walking Activity.

The selection of biomaterials for bearing in total hip arthroplasty is very important to avoid various risks of primary postoperative failure for patients. The current investigation attempts to analyze the Tresca stress of metal-on-metal bearings with three different materials, namely, cobalt chromium molybdenum (CoCrMo), stainless steel 316L (SS 316L), and titanium alloy (Ti6Al4V). We used computational simulations using a 2D axisymmetric finite element model to predict Tresca stresses under physiological conditions of the human hip joint during normal walking. The simulation results show that Ti6Al4V-on-Ti6Al4V has the best performance to reduce Tresca stress by 45.76% and 39.15%, respectively, compared to CoCrMo-on-CoCrMo and SS 316L-on-SS 316L.

Familiarity and genetic literacy among medical students in Indonesia.

BACKGROUND: There is a lack of genetic knowledge among health care professionals especially in some developing countries such as Indonesia. Based on our experience, genetic disorders receive less attention in medical education and professionals. This study aims to determine the familiarity and literacy of genetics among medical students in Indonesia. METHODS: A total of 1003 Indonesian medical (pre-clinical and clinical) students completed the Rapid Estimate of Adult Literacy in Genetics (REAL-G) questionnaire with a total score of seven for familiarity and eight for genetic literacy. The Mann-Whitney U test was used to compare the familiarity and genetic literacy scores between pre-clinical and clinical students. RESULTS: The average scores of familiarity and genetic literacy were 5.63 ± 0.96 and 6.37 ± 0.83, respectively. Genetic familiarity was higher (p = 0.043) among clinical students than pre-clinical students, while there was no significant difference in genetic literacy (p = 0.362) between pre-clinical and clinical students. Genetic familiarity does not impact the level of genetic literacy. However, medical students' genetic literacy is influenced by demographic characteristics, such as age, sex, university type, genetic learning experience, university accreditation, and university location. CONCLUSIONS: In general, Indonesian medical students have relatively good familiarity and literacy in genetics although further study is necessary to accurately measure the genetic familiarity and literacy in medical students and general public.

Attitudes of Indonesian health science undergraduates toward sexuality in individuals with intellectual disabilities.

BACKGROUND: Sexuality is a fundamental part of the lives of human beings. However, a significant inequality exists regarding the right of an individual with intellectual disabilities. AIMS: This study aimed to explore the attitudes of undergraduate health science students toward sexuality in individuals with intellectual disability (ID) in Indonesia. METHODS: A cross-sectional study was performed using the Indonesian version of Attitudes toward Sexuality Questionnaires in Intellectual Disability (ASQ-ID). This study involved 617 students in medical, psychology, and public health undergraduate programs. RESULTS: Among all participants (n = 617, male = 137, female = 480), the attitude towards self-control was found a significant difference among all three health science undergraduates (p = .01). The psychology students had the most favorable attitudes toward self-control compared to other students. The difference was found between medical and public health students and between public health and psychology students with p = .009 and p = .011, respectively. Religion was significantly affected for the non-reproductive sexual behavior subscale (p = .038). The religion was found to have significant effect on the attitude towards nonreproductive sexual behavior subscale (p = .038). CONCLUSIONS: Results show that Indonesian undergraduate students majoring in the health sciences have varying attitudes toward sexuality in individuals with ID. Medical and psychology students have more favorable attitudes toward self-control, whereas public health students have less favorable attitudes. Their religion influencing the attitudes toward nonreproductive sexual behavior.

Surveillance and prevalence of fragile X syndrome in Indonesia.

Fragile X syndrome (FXS) is the most prevalent inherited cause of intellectual disability (ID) and autism spectrum disorder (ASD). Many studies have been conducted over the years, however, in Indonesia there is relatively less knowledge on the prevalence of FXS. We reviewed all studies involving FXS screening and cascade testing of the high-risk population in Indonesia for two decades, to elucidate the prevalence, as well as explore the presence of genetic clusters of FXS in Indonesia. The prevalence of FXS in the ID population of Indonesia ranged between 0.9-1.9%, while in the ASD population, the percentage was higher (6.15%). A screening and cascade testing conducted in a small village on Java Island showed a high prevalence of 45% in the ID population, suggesting a genetic cluster. The common ancestry of all affected individuals was suggestive of a founder effect in the region. Routine screening and subsequent cascade testing are essential, especially in cases of ID and ASD of unknown etiology in Indonesia.

Repeat expansion and methylation-sensitive triplet-primed polymerase chain reaction for fragile X mental retardation 1 gene screening in institutionalised intellectually disabled individuals.

INTRODUCTION: Fragile X syndrome (FXS) is the most prevalent X-linked intellectual disability (ID) and a leading genetic cause of autism, characterised by cognitive and behavioural impairments. The hyperexpansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene leads to abnormal hypermethylation, resulting in the lack or absence of its protein. Tools for establishing the diagnosis of FXS have been extensively developed, including assays based on triplet-primed polymerase chain reaction (TP-PCR) for detection and quantification of the CGG trinucleotide repeat expansion, as well as determination of the methylation status of the alleles. This study aimed to utilise a simple, quick and affordable method for high sensitivity and specificity screening and diagnosis of FXS in institutionalised individuals with ID. METHODS: A total of 109 institutionalised individuals at the Center for Social Rehabilitation of Intellectual Disability Kartini, Temanggung, Central Java, Indonesia, were screened in a three-step process using FastFrax™ Identification, Sizing and Methylation Status Kits. RESULTS: Two samples that were classified as indeterminate with respect to the 41-repeat control at the identification step were subsequently determined to be non-expanded by both sizing and methylation status analyses. Two samples classified as expanded at the identification step were determined to carry full mutation expansions > 200 repeats that were fully methylated using sizing and methylation status analyses, respectively, yielding a disease prevalence of 1.83%. CONCLUSION: Repeat expansion and methylation-specific TP-PCR is practical, effective and inexpensive for the diagnosis of FXS, especially in high-risk populations of individuals with ID of undetermined aetiology.

Pathogenic variant in NFIX gene affecting three sisters due to paternal mosaicism.

We present a family with three girls presenting similar dysmorphic features, including overgrowth, intellectual disability, macrocephaly, prominent forehead, midface retrusion, strabismus, and scoliosis. Both parents were unaffected, suggesting the presence of an autosomal recessive syndrome. Following exome sequencing, a heterozygous nonsense variant was identified in the NFIX gene in all three siblings. The father appeared to have a low-grade (7%) mosaicism for this variant in his blood. Previously, de novo pathogenic variants in NFIX have been identified in Marshall-Smith syndrome and Malan syndrome, which share distinctive phenotypic features shared with the patients of the present family. This case emphasizes the importance of further molecular analysis especially in familial cases, to exclude the possibility of parental mosaicism.

Elevated FMR1-mRNA and lowered FMRP - A double-hit mechanism for psychiatric features in men with FMR1 premutations.

Fragile X syndrome (FXS) is caused by a full mutation of the FMR1 gene (>200 CGG repeats and subsequent methylation), such that there is little or no FMR1 protein (FMRP) produced, leading to intellectual disability (ID). Individuals with the premutation allele (55-200 CGG repeats, generally unmethylated) have elevated FMR1 mRNA levels, a consequence of enhanced transcription, resulting in neuronal toxicity and a spectrum of premutation-associated disorders, including the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS. In addition, the majority of these cases show psychiatric symptoms, including bipolar disorder, and/or psychotic features, which are rarely seen in those with just FXS.