Search

Abstract Background Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex. Methods To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family. Results We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females. Conclusions Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism’s genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism.

Background : Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex. Methods: To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family. Results: We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females. Conclusions: Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism's genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism. [ABSTRACT FROM AUTHOR]

Hypodontia is a developmental dental anomaly defined as the absence of one or more primary or permanent teeth excluding third molars. It can be associated with syndrome or nonsyndromic condition accompanied with other developmental dental anomalies like microdontia. Bilateral occurrence of hypodontia alongside microdontia is a rare condition. This case report presents a rare occurrence of bilateral hypodontia and microdontia in a nonsyndromic patient. Owing to its nonsyndromic background, other parameters like developmental delay, height, weight and body mass index are used as the predicting factors for the occurrence of hypodontia. Developmental milestones are one of the important factors in deriving the treatment plan. Treatment options in this case were directed at delaying the treatment until the eruption of the permanent successor teeth followed by the use of miniimplants for hypodontia, porcelain jacket crown for microdontia and the orthodontic treatment for final space closure.

Hypodontia is a developmental dental anomaly defined as the absence of one or more primary or permanent teeth excluding third molars. It can be associated with syndrome or nonsyndromic condition accompanied with other developmental dental anomalies like microdontia. Bilateral occurrence of hypodontia alongside microdontia is a rare condition. This case report presents a rare occurrence of bilateral hypodontia and microdontia in a nonsyndromic patient. Owing to its nonsyndromic background, other parameters like developmental delay, height, weight and body mass index are used as the predicting factors for the occurrence of hypodontia. Developmental milestones are one of the important factors in deriving the treatment plan. Treatment options in this case were directed at delaying the treatment until the eruption of the permanent successor teeth followed by the use of miniimplants for hypodontia, porcelain jacket crown for microdontia and the orthodontic treatment for final space closure. [ABSTRACT FROM AUTHOR]

Objective: To investigate cardiometabolic factors in children of parents with metabolic syndrome (MetS), and to determine the association of these factors among children and their parents. Methodology: This cross-sectional study was conducted as part of the baseline survey of a longitudinal study. According to inclusion/exclusion criteria, 800 children of parents with diagnosed MetS were selected by convenience sampling. Cardiometabolic data including fasting blood glucose (FBG), serum triglyceride (TG), total cholesterol (TC), body mass index (BMI), waist circumference (WC), and fat mass percentage (FMP) were collected and analyzed. Data regarding children's diet and their psychological state were also recorded by validated questionnaires. Mean of continuous variables were compared by one-way ANOVA and correlations between continuous variables were determined by the Pearson correlation test. Results: After excluding cases with missing data, information for 746 children (58% boys) and their parents was analyzed. Among children, TG was significantly correlated with BMI, WC, and FMP (p=0.001, r=0.24; p<0.0001, r=0.25; and p=0.01, r=0.19, respectively). Additionally, TC was significantly correlated with WC (p= 0.02). There were significant correlations between mother's FBG with children's BMI and WC (p=0.01, r=0.27; and p=0.00, r=0.29, respectively). Children of fathers and mothers with high BMI had significantly increased TC (p=0.04, and p=0.02, respectively). There was an inverse significant correlation between mood score and systolic blood pressure (p=0.03). There were also correlations between carbohydrates in children's diets and WC (p=0.02, r=0.34), and a near significant inverse correlation between nut consumption in diet and TC (p=0.05, r= -0.22). Conclusions: The current study showed the association of various factors on cardiometabolic risk factors in children and the relationship between these factors in children and in their parents. In addition to genetic predisposition, the familial aggregation of anthropometric measures underscores the role of obesogenic families in the development of cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

Cavernous angioma is one of several vascular malformations whose presentation is usually seizures, headaches, or neurological deficits. The frequency of such malformations is controversial and appears to be more common than once thought because of the availability of magnetic resonance imaging (MRI). A 16-year-old presented to an emergency department with the complaint of headaches and oral numbness. She was found to have mild dysarthria and right-sided hemiparesis. Computed tomography (CT) scan of the head revealed a large hemorrhage present in the left posterior frontal region with two smaller lesions in the vertebral hemispheres. MRI later confirmed the lesions to be compatible with cavernous angioma. The mother also complained of having a long history of headaches with numbness in her hands but had a negative CT scan. This raises the question of familial pattern, which has been well documented in the literature. A review of the literature looking at etiology, differential diagnosis, and management options is included. [Copyright &y& Elsevier]

Many people with the diagnosis of Asperger syndrome (AS) show poorly developed skills in understanding emotional messages. The present study addressed discrimination of speech prosody in children with AS at neurophysiological level. Detection of affective prosody was investigated in one-word utterances as indexed by the N1 and the mismatch negativity (MMN) of auditory event-related potentials (ERPs). Data from fourteen boys with AS were compared with those for thirteen typically developed boys. These results suggest atypical neural responses to affective prosody in children with AS and their fathers, especially over the RH, and that this impairment can already be seen at low-level information processes. Our results provide evidence for familial patterns of abnormal auditory brain reactions to prosodic features of speech. [ABSTRACT FROM AUTHOR]