The Detection of Environmental Influences on Academic Achievement Appears to Depend on the Analytic Approach.

One long-standing analytic approach in adoption studies is to examine correlations between features of adoptive homes and outcomes of adopted children (hereafter termed 'measured environment correlations') to illuminate environmental influences on those associations. Although results from such studies have almost uniformly suggested modest environmental influences on adopted children's academic achievement, other work has indicated that adopted children's achievement is routinely higher than that of their reared-apart family members, often substantially so. We sought to understand this discrepancy. We examined academic achievement and literacy-promotive features of the home in 424 yoked adoptive/biological families participating in the Early Growth and Development Study (EGDS; i.e., adopted children, adoptive mothers, birth mothers, and biological siblings of the adopted children remaining in the birth homes) using an exhaustive modeling approach. Results indicated that, as anticipated, adopted children scored up to a full standard deviation higher on standardized achievement tests relative to their birth mothers and reared-apart biological siblings. Moreover, these achievement differences were associated with differences in the literacy-promotive features of the adoptive and birth family homes, despite minimal measured environment correlations within adoptive families. A subsequent simulation study highlighted noise in measured environmental variables as an explanation for the decreased utility of measured environment correlations. We conclude that the field's heavy focus on measured environment correlations within adoptive families may have obscured detection of specific environmental effects on youth outcomes, and that future adoption studies should supplement their measured environment analyses with mean differences between reared-apart relatives.

Joint application of A-InDels and miniSTRs for forensic personal, full and half sibling identifications, and genetic differentiation analyses in two populations from China.

BACKGROUND: Previously, a novel multiplex system of 64 loci was constructed based on capillary electrophoresis platform, including 59 autosomal insertion/deletions (A-InDels), two Y-chromosome InDels, two mini short tandem repeats (miniSTRs), and an Amelogenin gene. The aim of this study is to evaluate the efficiencies of this multiplex system for individual identification, paternity testing and biogeographic ancestry inference in Chinese Hezhou Han (CHH) and Hubei Tujia (CTH) groups, providing valuable insights for forensic anthropology and population genetics research. RESULTS: The cumulative values of power of discrimination (CDP) and probability of exclusion (CPE) for the 59 A-InDels and two miniSTRs were 0.99999999999999999999999999754, 0.99999905; and 0.99999999999999999999999999998, 0.99999898 in CTH and CHH groups, respectively. When the likelihood ratio thresholds were set to 1 or 10, more than 95% of the full sibling pairs could be identified from unrelated individual pairs, and the false positive rates were less than 1.2% in both CTH and CHH groups. Biogeographic ancestry inference models based on 35 populations were constructed with three algorithms: random forest, adaptive boosting and extreme gradient boosting, and then 10-fold cross-validation analyses were applied to test these three models with the average accuracies of 86.59%, 84.22% and 87.80%, respectively. In addition, we also investigated the genetic relationships between the two studied groups with 33 reference populations using population statistical methods of FST, DA, phylogenetic tree, PCA, STRUCTURE and TreeMix analyses. The present results showed that compared to other continental populations, the CTH and CHH groups had closer genetic affinities to East Asian populations. CONCLUSIONS: This novel multiplex system has high CDP and CPE in CTH and CHH groups, which can be used as a powerful tool for individual identification and paternity testing. According to various genetic analysis methods, the genetic structures of CTH and CHH groups are relatively similar to the reference East Asian populations.

Associations between the number of siblings, parent-child relationship and positive youth development of adolescents in mainland China: A cross-sectional study.

BACKGROUND: Positive development plays an important role in youth when dealing with stressful circumstances. According to the resource dilution theory, adolescents with or without siblings may receive different levels of emotional and material resources from their parents. The purpose of this study is to examine the association between the positive development of adolescents in China today with their family characteristics such as the number of siblings. METHODS: A total of 2072 junior high and senior high school students (13 to 18 years old) in Chengdu, Sichuan, China, were investigated by cluster sampling. The Chinese Positive Youth Development scales (CPYDs) were used to measure positive youth development. The generalized linear model was used to explore the relationships among the number of siblings, parent-child relationships and positive youth development. RESULTS: Adolescents from only-child families had better performance on positive development (H = 21.87, P < 0.001) and better relationships with parents (H = 15.1, P < 0.05). The positive development of male and female adolescents does not significantly differ in families with different numbers of siblings. The generalized linear model showed that a positive parent-child relationship is positively correlated with adolescent positive development (P < 0.05). CONCLUSION: Positive youth development is not only associated with the number of siblings but also other modifiable familial factors. The positive relationship between parents and adolescents is of great practical value in daily life to improve youth development, and this might be the real lesson the resource dilution theory tells.

Comorbidities in women with polycystic ovary syndrome: a sibling study.

BACKGROUND: Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. METHODS: This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors. RESULTS: Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally. CONCLUSION: Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

Familial chylomicronemia syndrome: case reports of siblings with deletions of the GPIHBP1 gene.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). CASE PRESENTATION: A 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior. His elder brother also demonstrated an elevated triglyceride level of 2133 mg/dL at the age of 9. Lipoprotein electrophoresis revealed the presence of chylomicrons, an increase in the proportion of pre-beta lipoproteins, and low serum lipoprotein lipase levels. The patient's parents and first elder brother had stable lipid profiles. For suspected FCS, genetic testing was performed using the next-generation sequencing-based analysis of 31 lipid metabolism-associated genes, which revealed no pathogenic variants. However, copy number variant screening using sequencing depth information suggested large heterozygous deletion encompassing all the coding exons of GPIHBP1. A real-time quantitative polymerase chain reaction was performed to validate the deletion site. The results showed that the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. During the follow-up period of 17 months, the patient did not develop pancreatitis, following dietary intervention. CONCLUSION: These siblings' case of familial chylomicronemia syndrome caused by rare GPIHBP1 deletions highlight the implementation of copy number variants-beyond next-generation sequencing-as an important consideration in diagnosis. Accurate genetic diagnosis is necessary to establish the etiology of severe hypertriglyceridemia, which increases the risk of pancreatitis.

Multilocus pathogenic variants contribute to intrafamilial clinical heterogeneity: a retrospective study of sibling pairs with neurodevelopmental disorders.

BACKGROUND: Multilocus pathogenic variants (MPVs) are genetic changes that affect multiple gene loci or regions of the genome, collectively leading to multiple molecular diagnoses. MPVs may also contribute to intrafamilial phenotypic variability between affected individuals within a nuclear family. In this study, we aim to gain further insights into the influence of MPVs on a disease manifestation in individual research subjects and explore the complexities of the human genome within a familial context. METHODS: We conducted a systematic reanalysis of exome sequencing data and runs of homozygosity (ROH) regions of 47 sibling pairs previously diagnosed with various neurodevelopmental disorders (NDD). RESULTS: We found siblings with MPVs driven by long ROH regions in 8.5% of families (4/47). The patients with MPVs exhibited significantly higher FROH values (p-value = 1.4e-2) and larger total ROH length (p-value = 1.8e-2). Long ROH regions mainly contribute to this pattern; the siblings with MPVs have a larger total size of long ROH regions than their siblings in all families (p-value = 6.9e-3). Whereas the short ROH regions in the siblings with MPVs are lower in total size compared to their sibling pairs with single locus pathogenic variants (p-value = 0.029), and there are no statistically significant differences in medium ROH regions between sibling pairs (p-value = 0.52). CONCLUSION: This study sheds light on the significance of considering MPVs in families with affected sibling pairs and the role of ROH as an adjuvant tool in explaining clinical variability within families. Identifying individuals carrying MPVs may have implications for disease management, identification of possible disease risks to different family members, genetic counseling and exploring personalized treatment approaches.

Using emulated clinical trials to investigate the risk of being diagnosed with psychiatric ill health following the cancer diagnosis of a sibling.

BACKGROUND: The sibling bond is often the longest relationship in an individual's life, spanning both good and bad times. Focusing on the latter, we investigated whether a cancer diagnosis in one adult sibling is predictive of psychiatric illness in the other, and if any such effect differs according the 'sociodemographic closeness' between the siblings in terms of sex, age, education, marital status and residence. METHODS: We used hospital records to identify psychiatric diagnoses (2005-2019) in a Swedish total-population cohort born in 1953, and cancer diagnoses (2005-2017) in their full siblings. By means of emulated clinical trials, the cohort member's risk of a diagnosis within two years following a first exposure (or non-exposure) to a sibling's cancer was analyzed through Cox regression. RESULTS: Exposed cohort members had a higher risk of psychiatric diagnosis than unexposed (HR = 1.15; CI: 1.08-1.23), with men displaying a higher risk (1.19; CI: 1.09-1.31) than women (HR = 1.11; CI: 1.01-1.22). Sub-analyses of the exposed group showed that women with a cancer-stricken sister had a higher risk of adverse psychiatric outcomes (HR = 1.31; CI: 1.07-1.61) than women with a cancer-stricken brother. Furthermore, unmarried cohort members ran a higher risk, both when the cancer-stricken sibling was married (HR = 2.03; CI: 1.67-2.46) and unmarried (HR = 2.61; CI: 2.16-3.15), than in cases where both siblings were married. No corresponding difference were detected for 'closeness' in age, education and residence. CONCLUSIONS: In line with theories of linked lives, our findings suggest that negative events in one sibling's life tend to 'spill over' on the other sibling's wellbeing, at least during the 15-year-long period leading up to retirement age.

Automated Single-Sperm Selection Software (SiD) during ICSI: A Prospective Sibling Oocyte Evaluation.

The computer-assisted program SiD was developed to assess and select sperm in real time based on motility characteristics. To date, there are limited studies examining the correlation between AI-assisted sperm selection and ICSI outcomes. To address this limit, a total of 646 sibling MII oocytes were randomly divided into two groups as follows: the ICSI group (n = 320): ICSI performed with sperm selected by the embryologist and the ICSI-SiD group (n = 326): ICSI performed with sperm selected using SiD software. Our results show a non-significant trend towards improved outcomes in the ICSI-SiD group across various biological parameters, including fertilization, cleavage, day 3 embryo development, blastocyst development, and quality on day 5. Similarly, we observed a non-significant increase in these outcomes when comparing both groups with sperm selection performed by a junior embryologist. Embryo development was monitored using a timelapse system. Some fertilization events happen significantly earlier when SiD is used for ICSI, but no significant difference was observed in the ICSI-SiD group for other timepoints. We observed comparable cumulative early and clinical pregnancy rates after ICSI-SiD. This preliminary investigation illustrated that employing the automated sperm selection software SiD leads to comparable biological outcomes, suggesting its efficacy in sperm selection.

An analysis of the accuracy of retrospective birth location recall using sibling data.

Many surveys ask participants to retrospectively record their location of birth. This paper examines the accuracy of such data in the UK Biobank using a sample of full siblings. Comparison of reported birth locations for siblings with different age gaps allows us to estimate the probabilities of household moves and of misreported birth locations. Our first contribution is to show that there are inaccuracies in retrospective birth location data, showing a sizeable probability of misreporting, with 28% of birth coordinates, 16% of local districts and 6% of counties of birth being incorrectly reported. Our second contribution is to show that such error can lead to substantial attenuation bias when investigating the impacts of location-based exposures, especially when there is little spatial correlation and limited time variation in the exposure variable. Sibling fixed effect models are shown to be particularly vulnerable to the attenuation bias. Our third contribution is to highlight possible solutions to the attenuation bias and sensitivity analyses to the reporting error.

Educational attainment, family background and the emergence of pain gradients in adulthood.

Current studies have indicated that the number of individuals living with pain has risen in recent years, with nearly half of all adults in some countries living with some form of pain. Such trends have prompted researchers to explore differences in pain across different sociodemographic groups, with a dominant focus on educational attainment. However, much of the studies fail to consider the confounding role of early life characteristics, such as family background. Using data on over 400,000 individuals from the UK Biobank, we look at how educational attainment is associated with nine different domains of pain (headache, facial, neck, back, hip, knee, stomach, all over, and no pain). Ultimately, we find that compared to those with no educational credentials, education is associated with anywhere between a 0.1-15% change in the likelihood of reporting pain, depending on pain type and education level, with the greatest change occurring in those with the highest level. Yet, when accounting for family background characteristics in the form of sibling fixed effects, nearly all relationships between education and pain fell by either 50% or were eliminated. We ultimately conclude that failure to consider early life characteristics, such as family background characteristics may lead to inflated estimates of pain, and that future research should delve into early life exposures and their influence on pain in adulthood.

Reduced toxicity matched sibling bone marrow transplant results in excellent outcomes for severe congenital neutropenia.

Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in ELANE, impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with ELANE-mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT.

Gut microbial and clinical characteristics of individuals with autism spectrum disorder differ depending on the ecological structure of the gut microbiome.

Understanding the relationship between the gut microbiome and autism spectrum disorder (ASD) is challenging due to the heterogeneous nature of ASD. Here, we analyzed the microbial and clinical characteristics of individuals with ASD using enterotypes. A total of 456 individuals participated in the study, including 249 participants with ASD, 106 typically developing siblings, and 101 controls. The alpha and beta diversities of the ASD, sibling, and control groups did not show significant differences. Analysis revealed a negative association between the Bifidobacterium longum group and the Childhood Autism Rating Scale, as well as a negative association between the Streptococcus salivarus group and the Social Responsiveness Scale (SRS) within the ASD group. When clustered based on microbial composition, participants with ASD exhibited two distinct enterotypes, E1 and E2. In the E2 group, the SRS score was significantly higher, and the Vineland Adaptive Behavior Scale score was significantly lower compared to the E1 group. Machine learning results indicated that the microbial species predicting SRS scores were distinct between the two enterotypes. Our study suggests that the microbial composition in individuals with ASD exhibits considerable variability, and the patterns of associations between the gut microbiome and clinical symptoms may vary depending on the enterotype.

Well-differentiated liposarcomas and dedifferentiated liposarcomas: Systemic treatment options for two sibling neoplasms.

Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) account for 60 % of all liposarcomas, reflecting the heterogeneity of this type of sarcoma. Genetically, both types of liposarcomas are characterized by the amplification of MDM2 and CDK4 genes, which indicates an important molecular event with diagnostic and therapeutic relevance. In both localized WDLPS and DDLPS of the retroperitoneum and the extremities, between 25 % and 30 % of patients have local or distant recurrence, even when perioperatively treated, with clear margins present. The systemic treatment of WDLPS and DDLPS remains a challenge, with anthracyclines as the gold standard for first-line treatment. Several regimens have been tested with modest results regarding their efficacy. Herein we discuss the systemic treatment options for WDLPS and DDLPS and review their reported clinical efficacy results.

Birth Spacing and Parents' Physical and Mental Health: An Analysis Using Individual and Sibling Fixed Effects.

An extensive literature has examined the relationship between birth spacing and subsequent health outcomes for parents, particularly for mothers. However, this research has drawn almost exclusively on observational research designs, and almost all studies have been limited to adjusting for observable factors that could confound the relationship between birth spacing and health outcomes. In this study, we use Norwegian register data to examine the relationship between birth spacing and the number of general practitioner consultations for mothers' and fathers' physical and mental health concerns immediately after childbirth (1-5 and 6-11 months after childbirth), in the medium term (5-6 years after childbearing), and in the long term (10-11 years after childbearing). To examine short-term health outcomes, we estimate individual fixed-effects models: we hold constant factors that could influence parents' birth spacing behavior and their health, comparing health outcomes after different births to the same parent. We apply sibling fixed effects in our analysis of medium- and long-term outcomes, holding constant mothers' and fathers' family backgrounds. The results from our analyses that do not apply individual or sibling fixed effects are consistent with much of the previous literature: shorter and longer birth intervals are associated with worse health outcomes than birth intervals of approximately 2-3 years. Estimates from individual fixed-effects models suggest that particularly short intervals have a modest negative effect on maternal mental health in the short term, with more ambiguous evidence that particularly short or long intervals might modestly influence short-, medium-, and long-term physical health outcomes. Overall, these results are consistent with small to negligible effects of birth spacing behavior on (non-pregnancy-related) parental health outcomes.

Extra Nestlings That Are Condemned to Die Increase Reproductive Success in Hoopoes.

AbstractThe adaptive value of routinely laying more eggs than can be successfully fledged has intrigued evolutionary biologists for decades. Extra eggs could, for instance, be adaptive as insurance against hatching failures. Moreover, because recent literature demonstrates that sibling cannibalism is frequent in the Eurasian hoopoe (Upupa epops), producing extra offspring that may be cannibalized by older siblings might also be adaptive in birds. Here, directed to explore this possibility in hoopoes, we performed a food supplementation experiment during the laying period and a clutch size manipulation during the hatching stage. We found that females with the food supplement laid on average one more egg than control females and that the addition of a close-to-hatch egg at the end of the hatching period increased the intensity of sibling cannibalism and enhanced fledging success in hoopoe nests. Because none of the extra nestlings from the experimental extra eggs survived until fledging, these results strongly suggest that hoopoes obtain fitness advantages by using temporarily abundant resources to produce additional nestlings that will be cannibalized. These results therefore suppose the first experimental demonstration of the nutritive adaptive function of laying extra eggs in vertebrates with parental care.

Being a sibling of a youth with a neurodisability: A qualitative study about the roles and responsibilities during the transition to adulthood.

BACKGROUND: During the transition to adulthood, a common challenge that youth with a neurodisability may experience is learning how to navigate services in the adult care system. During this transition youth may rely on their families, including siblings, for support. However, delineation of sibling roles and responsibilities during this transition period are unclear. This study aims to identify the roles and responsibilities that siblings perceive to have with their sibling with a neurodisability during the transition to adulthood, and describe the decision-making process of how siblings chose these roles. METHODS: In this descriptive qualitative case study, siblings were eligible to participate if they were between 14 to 40 years old, had a sibling between 14 to 21 years with a childhood-onset neurodisability and spoke English. Semi-structured interviews augmented by techniques of photo elicitation and relational maps were conducted. Reflexive thematic analysis was applied to identify sibling roles, as well as the emotional and decision-making process associated with these roles. Our team partnered with siblings with lived experience in all study phases. RESULTS: Nineteen participants (median age = 19 years, range = 14 to 33 years) from 16 unique families were interviewed. Six unique roles were described: friend, role model/mentor, protector, advocate, supporter, or caregiver. The emotions that siblings experienced with each role, also known as emotional responsibility, were categorized into levels of low, medium or high. Siblings also described a four-phase decision-making process for their roles: (1) acquiring knowledge; (2) preparing plans; (3) making adjustments; and (4) seeking support. Intrapersonal characteristics, including personal identity, values and experiences, influenced roles assumed by siblings. CONCLUSIONS: Siblings identified needing support as they process their decisions and emotional responsibility in their roles when their sibling with a neurodisability is transitioning to adulthood. Resources should be developed or further enhanced to support siblings.

Quality of life of families and siblings of children and adolescents with meningomyelocele.

BACKGROUND: Children with meningomyelocele may require continuous care. Consequently, there is a risk for caregiver burden and impact on family quality of life (QoL), including siblings' QoL. Some studies analysed caregivers' burden and family QoL separately. However, none of these studies evaluated siblings' QoL and the associations between these three dimensions. This study investigated the associations between caregivers' burden, family QoL and siblings' QoL in Brazilian families of children with meningomyelocele and its correlations with sociodemographic, functional and clinical variables. Siblings' QoL was specifically assessed using as a parameter the QoL of typically developed Brazilian children. METHODS: One hundred and fifty families, 150 caregivers and 68 siblings completed the Family Quality of Life Scale, Burden Interview, KIDSCREEN-27 Child and Adolescent Version and Parents Version questionnaires. RESULTS: Most families and caregivers reported a high family QoL and a low caregiver burden. Family QoL was significantly lower as caregivers' burden increased. Caregiver's burden was significantly lower with increasing family QoL levels. Self-reported siblings' QoL was significantly worse than that of typically developed peers. There were no significant differences between self and parent-reported siblings' QoL. Self-reported siblings' QoL was significantly worse as their age increased and better with increasing family QoL levels. Parent-reported siblings' QoL was significantly worse with increasing levels of caregiver's burden and significantly better as family QoL increased. There were no significant associations with functional and clinical variables. CONCLUSIONS: Despite the cross-sectional nature of the available data precludes any statements of causality, our results reinforce the relevance of knowing the factors that influence the QoL of families and siblings of children and adolescents with meningomyelocele and the relevance of actions aimed at reducing caregivers' burden, improving family QoL and meeting siblings' individual needs. Future multicenter studies may validate the generalizability of our findings.

Trafficking in Disease: More Evidence for Air Pollution-Parkinson's Association.

Research using Sister Study data has implicated nitrogen dioxide (vehicle exhaust is a major source), and possibly fine particulate matter, in increased risk for Parkinson's disease.

Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism.

ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.

A pathogenic P4HTM gene variant in two brothers with autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental condition that involves limitations in social communication and various stereotypical repetitive behaviors. Genetic and environmental factors both play a role in the etiology. Numerous genetic syndromes accompanying autism spectrum disorders have been reported. Hypoventilation, hypotonia, intellectual disability, epilepsy, eye abnormality (HIDEA) syndrome is a rare genetic condition consisting of a combination of features such as hypoventilation, hypotonia, intellectual disability, eye abnormalities, and epilepsy. Very few cases of HIDEA syndrome have been reported in the literature to date. To the best of our knowledge, no cases of comorbid autism spectrum disorder and HIDEA syndrome have previously been reported. This report describes two brothers with a pathogenic P4HTM gene variant and autism spectrum disorder. One was diagnosed with HIDEA syndrome, while the other was a healthy carrier.