Dataset Information

Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype.

ABSTRACT: Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10-12.

SUBMITTER: Balasubramanian M

PROVIDER: S-EPMC8115148 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Internet Gaming Disorder (IGD) is characterized by impairments in social communication and the avoidance of social contact. Facial expression processing is the basis of social communication. However, few studies have investigated how individuals with IGD process facial expressions, and whether they have deficits in emotional facial processing remains unclear. The aim of the present study was to explore these two issues by investigating the time course of emotional facial processing in individuals with IGD. A backward masking task was used to investigate the differences between individuals with IGD and normal controls (NC) in the processing of subliminally presented facial expressions (sad, happy, and neutral) with event-related potentials (ERPs). The behavioral results showed that individuals with IGD are slower than NC in response to both sad and neutral expressions in the sad-neutral context. The ERP results showed that individuals with IGD exhibit decreased amplitudes in ERP component N170 (an index of early face processing) in response to neutral expressions compared to happy expressions in the happy-neutral expressions context, which might be due to their expectancies for positive emotional content. The NC, on the other hand, exhibited comparable N170 amplitudes in response to both happy and neutral expressions in the happy-neutral expressions context, as well as sad and neutral expressions in the sad-neutral expressions context. Both individuals with IGD and NC showed comparable ERP amplitudes during the processing of sad expressions and neutral expressions. The present study revealed that individuals with IGD have different unconscious neutral facial processing patterns compared with normal individuals and suggested that individuals with IGD may expect more positive emotion in the happy-neutral expressions context.• The present study investigated whether the unconscious processing of facial expressions is influenced by excessive online gaming. A validated backward masking paradigm was used to investigate whether individuals with Internet Gaming Disorder (IGD) and normal controls (NC) exhibit different patterns in facial expression processing.• The results demonstrated that individuals with IGD respond differently to facial expressions compared with NC on a preattentive level. Behaviorally, individuals with IGD are slower than NC in response to both sad and neutral expressions in the sad-neutral context. The ERP results further showed (1) decreased amplitudes in the N170 component (an index of early face processing) in individuals with IGD when they process neutral expressions compared with happy expressions in the happy-neutral expressions context, whereas the NC exhibited comparable N170 amplitudes in response to these two expressions; (2) both the IGD and NC group demonstrated similar N170 amplitudes in response to sad and neutral faces in the sad-neutral expressions context.• The decreased amplitudes of N170 to neutral faces than happy faces in individuals with IGD might due to their less expectancies for neutral content in the happy-neutral expressions context, while individuals with IGD may have no different expectancies for neutral and sad faces in the sad-neutral expressions context.

Project description:BACKGROUND:Reduction or differences in facial expression are a core diagnostic feature of autism spectrum disorder (ASD), yet evidence regarding the extent of this discrepancy is limited and inconsistent. Use of automated facial expression detection technology enables accurate and efficient tracking of facial expressions that has potential to identify individual response differences. METHODS:Children and adults with ASD (N = 124) and typically developing (TD, N = 41) were shown short clips of "funny videos." Using automated facial analysis software, we investigated differences between ASD and TD groups and within the ASD group in evidence of facial action unit (AU) activation related to the expression of positive facial expression, in particular, a smile. RESULTS:Individuals with ASD on average showed less evidence of facial AUs (AU12, AU6) relating to positive facial expression, compared to the TD group (p < .05, r = -?0.17). Using Gaussian mixture model for clustering, we identified two distinct distributions within the ASD group, which were then compared to the TD group. One subgroup (n = 35), termed "over-responsive," expressed more intense positive facial expressions in response to the videos than the TD group (p < .001, r = 0.31). The second subgroup (n = 89), ("under-responsive"), displayed fewer, less intense positive facial expressions in response to videos than the TD group (p < .001; r = -?0.36). The over-responsive subgroup differed from the under-responsive subgroup in age and caregiver-reported impulsivity (p < .05, r = 0.21). Reduced expression in the under-responsive, but not the over-responsive group, was related to caregiver-reported social withdrawal (p < .01, r = -?0.3). LIMITATIONS:This exploratory study does not account for multiple comparisons, and future work will have to ascertain the strength and reproducibility of all results. Reduced displays of positive facial expressions do not mean individuals with ASD do not experience positive emotions. CONCLUSIONS:Individuals with ASD differed from the TD group in their facial expressions of positive emotion in response to "funny videos." Identification of subgroups based on response may help in parsing heterogeneity in ASD and enable targeting of treatment based on subtypes. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02299700. Registration date: November 24, 2014.

Dataset Information

Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets