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Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Environmental pollutants may contribute to the etiology of ASD, but studies of perfluoroalkyl substances (PFAS) have shown conflicting results., Objectives: We assessed associations between cord blood concentrations of PFAS with autistic traits at age seven years in a Singaporean birth cohort., Methods: We measured cord blood concentrations of eight PFAS in a sample of 430 mother-child pairs from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. We assessed autistic traits using the Social Responsiveness Scale Second Edition (SRS-2) and its sub-scores, in which higher scores indicate more autistic traits. We estimated covariate-adjusted associations between the PFAS and SRS-2 scores using Bayesian weighted quantile sum (BWQS) regression models for the PFAS mixtures and multivariable regressions for single PFAS. We additionally evaluated effect modification by biological sex., Results: We observed a positive association between the PFAS mixture and SRS-2 cognition sub-scores (β per SD increase = 1.25 points, 95% CI -0.03, 2.40). Perfluorononanoic acid (PFNA) was the strongest contributor to the mixture effect. In single PFAS models, exposure to PFNA was associated with a higher SRS-2 total score (β = 0.93 points, 95% CI 0.29, 1.58), cognition sub-score (β = 1.26 points, 95% CI 0.55, 1.97), communication sub-score (β = 0.88 points, 95% CI 0.20, 1.56), and restrictive and repetitive behaviors sub-score (β = 0.93 points, 95% CI 0.23, 1.63). We also observed evidence of effect modification by sex for perfluoroundecanoic acid (PFUnDA) for the total score (p-effect modification [EM] = 0.03), cognition sub-score (p-EM = 0.03), and communication sub-score (p-EM = 0.04), with negative associations seen in females and null associations in males., Discussion: Cord blood PFAS concentrations were positively associated with autistic traits measured by SRS-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation., Objectives: We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII)., Methods: We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011-2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests., Results: The median (interquartile range) of blood metals were 0.38 μg/L (0.35), 14.70 μg/L (11.70), and 8.74 μg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (-0.04; 95% confidence interval [CI] = -0.09, 0.02), CERAD (-0.04; 95% CI = -0.12, 0.03), animal fluency (-0.02; 95% CI, -0.11, 0.06), and DSST (-0.05; 95% CI = -0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women., Conclusions: Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Introduction: Per and polyfluoroalkyl substances (PFAS), including perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA), were detected in the community water supply of Paulsboro New Jersey in 2009., Methods: A cross-sectional study enrolled 192 claimants from a class-action lawsuit, not affiliated with this study, who had been awarded a blood test for 13 PFAS. Study participants provided their blood test results and completed a survey about demographics; 105 participants also completed a health survey. Geometric means, 25th, 50th, 75th, and 95th percentiles of exposure of PFNA blood serum concentrations were compared to that of the 2013-2014 NHANES, adjusted for reporting level. Associations between PFNA, PFOA, PFOS, and PFHxS and self-reported health outcomes were assessed using logistic regression., Results: PFNA serum levels were 285% higher in Paulsboro compared with U.S. residents. PFNA serum levels were higher among older compared with younger, and male compared to female, Paulsboro residents. After adjustment for potential confounding, there was a significant association between increased serum PFNA levels and self-reported high cholesterol (OR: 1.15, 95% CI: 1.02, 1.29)., Discussion/conclusion: Further investigation into possible health effects of PFAS exposure in Paulsboro and other community settings is warranted. Since exposure has ceased, toxicokinetics of PFAS elimination should be explored.

The Prader-Willi syndrome (PWS) usually results from a paternal deletion of 15q11-q13 or maternal disomy for chromosome 15. Reduced pigmentation of skin, hair, and eyes is common in PWS and was suggested previously to be associated with the 15q11-q13 deletion. The P gene, located in this same region, is associated with OCA2, an autosomal recessive disorder that is the most frequent form of tyrosinase-positive oculocutaneous albinism. We studied 28 individuals with PWS and found that hemizygosity for the P gene was significantly correlated with the occurrence of hypopigmentation among PWS patients. However, we found little or no relationship between the occurrence of hypopigmentation and the polymorphism haplotype of the intact P allele. Thus, our results indicate that hypopigmentation is likely the result of deletion of the P gene in the context of PWS but do not support the linked hypothesis that hypopigmentation results from hemizygosity for variant P alleles with reduced function.

The aim of this study was to clarify the nature of the sleep abnormalities (excessive daytime sleepiness [EDS] and rapid eye movement [REM] sleep alterations) in Prader-Willi; Syndrome (PWS). Eight PWS patients, 15 normal, 16 narcoleptic, and 16 obese subjects were recorded in the sleep laboratory, both during daytime and nighttime. A principal-finding was that EDS in PWS was associated with an increased amount and depth of sleep. In PWS patients with EDS, compared to those PWS patients without EDS or the narcoleptic, obese, and normal groups, there were significant decreases in wakefulness and increases in percentage of sleep time (ST) and slow-wave sleep (SWS) both during daytime and nighttime testing. Also, in the adult PWS subjects (n = 6), in contrast to normal narcoleptic subjects, intensity of EDS was correlated with increased nocturnal percentage of ST and SWS and % SWS was positively correlated with % ST (both during daytime and nighttime testing). Another principal finding was that in PWS there is a unique alteration of the distribution of REM sleep in relation to controls. PWS patients with EDS or shortened nocturnal REM latencies showed a significantly increased number of REM periods, and a decreased average REM interval between REM periods compared to PWS patients with nonshortened nocturnal REM latencies or to the three control groups. Our data suggest that EDS and REM abnormalities in PWS are not manifestations of a narcoleptic-type syndrome or consequences of obesity. We propose that generalized 24-hour hypoarousal is the primary mechanism underlying the sleep abnormalities in PWS patients.

To assess whether sleep abnormalities are related to the genetic abnormalities in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) and determined the chromosome 15 genotypes in eight patients with PWS. Four patients demonstrated sleep onset REM periods (SOREM), and five met the objective polysomnographic criteria for severe or moderate excessive daytime sleepiness (EDS). Three of the four patients with SOREM displayed a paternally derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal uniparental heterodisomy in this chromosomal region (UPD). Two of the four patients that did not display SOREM carried paternally derived deletions; the remaining two demonstrated UPD. Four of the five patients with EDS displayed paternal deletions, and the fifth exhibited UPD. One of three patients without evidence of EDS demonstrated paternal deletion; the remaining two showed UPD. Although neither EDS nor SOREM was not consistently associated with a specific genetic abnormality, these phenotypes may be more common in patients with paternal deletions than in those UPD. Sleep abnormalities in PWS cannot be explained by a single genetic model.

We have studied a large Mennonite kindred in which 20 members were affected with Hirschsprung disease (HSCR), 5 of whom had one or more manifestations of Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest migration/differentiation, this large pedigree with apparent cosegregation of HSCR and WS2 offered an opportunity to search for linkage between these loci, candidate genes, and random DNA markers, particularly in view of recent discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung disease (c-ret). We have examined the following possible linked markers in 69 relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to ABO blood groups which have shown weak linkage to WS; and the beta 1 GABA receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred was excluded, demonstrating that there is at least one further locus for HSCR other than c-ret.

Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology characterized by the absence of enteric ganglia in the distal colon. We have ascertained a large, inbred, Mennonite kindred which demonstrates a high incidence of Hirschsprung disease (HSCR). Genealogical analysis of all kinship relationships identified a single common ancestral couple for all parents of affected offspring. Segregation analysis yielded a segregation ratio of 10.67% for males and 5.45% for females. We searched for locations of the gene(s) responsible for HSCR in this pedigree by genotyping three small multicase families and locating genomic regions demonstrating identity-by-descent followed by linkage disequilibrium analysis of 28 additional nuclear families. Based on this novel strategy, we report the mapping of a new locus for HSCR to chromosome 13q22. Nine microsatellite markers spanning 10 cM in this region were genotyped on thirty-one nuclear families. Significant nonrandom association was detected with alleles at markers D13S162, D13S160, D13S170, and AFM240zg9. In addition, our studies reveal preliminary evidence for a genetic modifier of HSCR in this kindred on chromosome 21q22.

Brothers were affected with severe congenital contractures, multiple cutaneous manifestations of ectodermal dysplasia, cleft lip/palate, and psychomotor and growth impairment. High resolution prometaphase chromosomes were normal. Molecular studies of DNA markers, closely flanking the X-linked hypohidrotic ectodermal dysplasia locus, did not show evidence of a submicroscopic deletion from the Xq12-q13 region. The parents and a normal sister exhibited none of these findings. This constellation of anomalies appears to represent a unique AR or XLR syndrome.

Background: Prader-Willi syndrome is a genetic disorder characterized by infantile hypotonia, obesity, hypogonadism, and mental retardation, but it is difficult to diagnose clinically in infants and young children. In about two thirds of patients, a cytogenetically visible deletion can be detected in the paternally derived chromosome 15 (15q11q13). Recently, patients with Prader-Willi syndrome have been described who do not have the cytogenetic deletion but instead have two copies of the 15q11q13 region that are inherited from the mother (with none inherited from the father). This unusual form of inheritance is known as maternal uniparental disomy. Using molecular genetic techniques, we sought to determine the frequency of uniparental disomy in Prader-Willi syndrome., Methods: We performed molecular analyses using DNA markers within 15q11q13 and elsewhere on chromosome 15 in 30 patients with Prader-Willi syndrome who had no cytogenetically visible deletion. We also studied their parents. Three patients with Prader-Willi syndrome who had a cytogenetic deletion served as controls., Results: In 18 of the 30 patients without a cytogenetic deletion (60 percent), we demonstrated the presence of maternal uniparental disomy for chromosome 15 and its association with advanced maternal age. In another eight patients (27 percent), we identified large molecular deletions. The remaining four patients (13 percent) had evidence of normal biparental inheritance for chromosome 15; three of these patients were the only ones in the study who had some atypical clinical features., Conclusions: In about 20 percent of all cases, Prader-Willi syndrome results from the inheritance of both copies of chromosome 15 from the mother (maternal uniparental disomy). With the combined use of cytogenetic and molecular techniques, the genetic basis of Prader-Willi syndrome can be identified in up to 95 percent of patients.