Genetic analysis of very obese children with autism spectrum disorder

Cortes, Herman D.; Wevrick, Rachel

doi:10.1007/s00438-018-1418-5

Cited by 9 publications

(4 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we focused on the ‘adipo-brain axis’ as a potential pathophysiology of ASD by examining the serum levels of adipokines and other metabolic markers. Genome-wide association studies have repeatedly reported on the overlap between genetic risk variants in ASD and obesity ( Bachmann-Gagescu et al , 2010 ; Walters et al , 2010 ; Shinawi et al , 2011 ; Lee et al , 2012 ; Sharma et al , 2013 ; Cortes and Wevrick, 2018 ; Grove et al , 2019 ). In addition, a low birth weight has been reported to increase the risk of ASD ( Schendel and Bhasin, 2008 ; Lampi et al , 2012 ).…”

Section: Discussionmentioning

confidence: 99%

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder

Maekawa

Ohnishi

Toyoshima

et al. 2020

Brain Communications

View full text Add to dashboard Cite

Autism spectrum disorder is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, as well as repetitive and characteristic patterns of behavior. Although the pathogenesis of autism spectrum disorder is unknown, being overweight or obesity during infancy and low weight at birth are known as risks, suggesting a metabolic aspect. In this study, we investigated adipose tissue development as a pathophysiological factor of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in autism spectrum disorder children (n = 123) and typically developing children (n = 92) at 4–12 years of age. Among multiple measures exhibiting age-dependent trajectories, the leptin levels displayed different trajectory patterns between autism spectrum disorder and typically developing children, supporting an adipose tissue-dependent mechanism of autism spectrum disorder. Of particular interest, the levels of FABP4 (fatty acid binding protein 4) were significantly lower in autism spectrum disorder children than in typically developing subjects, at preschool age (4–6 years old: n = 21 for autism spectrum disorder and n = 26 for typically developing). The receiver operating characteristic curve analysis discriminated autism spectrum disorder children from typically developing children with a sensitivity of 94.4% and a specificity of 75.0%. We re-sequenced the exons of the FABP4 gene in a Japanese cohort comprising 659 autism spectrum disorder and 1,000 control samples, and identified two rare functional variants in the autism spectrum disorder group. The Trp98Stop, one of the two variants, was transmitted to the proband from his mother with a history of depression. The disruption of the Fabp4 gene in mice evoked autism spectrum disorder -like behavioral phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in the postmortem brains of autism spectrum disorder subjects. The Fabp4 knockout mice had an altered fatty acid composition in the cortex. Collectively, these results suggest that an “adipo-brain axis” may underlie the pathophysiology of autism spectrum disorder, with FABP4 as a potential molecule for use as a biomarker.

show abstract

Section: Discussionmentioning

confidence: 99%

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder

Maekawa

Ohnishi

Toyoshima

et al. 2020

Brain Communications

View full text Add to dashboard Cite

show abstract

“…In another study, a genetic analysis revealed loss-offunction mutations in 20 genes, including the VCP variant (dnLGD) that described children with autism spectrum disorders who were highly obese and had low IQ scores. In that study, the investigators detected genetic lesions and attempted to find perturbed biochemical processes in a group of ASD children with obesity (Cortes and Wevrick 2018). Numerous issues, such as seizures, sleep difficulties, obesity and metabolic diseases, hormonal dysfunctions, and nutritional deficiencies have been linked to a greater number of adolescents suffering from ASD (Bauman 2010).…”

Section: Val103ilementioning

confidence: 99%

Identification of MC4R and VCP Genetic Variants in Two Pakistani Families Showing Symptoms of Diabetes, Hyperphagia, Seizures, and Obesity

Naudhani,

Bazai,

Mehmood Ul Hassan

et al. 2023

Mol. Med. Com.

View full text Add to dashboard Cite

Variations in the melanocortin 4 receptor (MC4R) are most commonly associated with serious early-stage monogenic obesity. The valosin-containing protein (VCP) gene, also referred to as p97, produces the ubiquitous, crucial, and multifunctional protein VCP, involved in a wide range of cellular processes, including endoplasmic reticulum-associated degradation (ERAD), degradation of lysosomal protein, and degradation of the proteasome-mediated protein. In the present study, we investigated two Pakistani families enrolled from Sibi, Pakistan, for variation in MC4R and VCP genes. Clinical symptoms involved obesity, hyperphagia, and diabetes in Family 1. Obesity with autism spectrum disorder (ASD), hyperphagia, diabetes, seizure, gastrointestinal, and sleep disorders were found in Family 2. Additionally, blood samples were collected and DNA extraction was performed. Subsequent molecular analysis was conducted to identify mutations. Clinical and genetic results were analyzed, and the segregation of MC4R and VCP gene variants in the families helped to make the diagnosis of the disease. For the identification of variations, we conducted whole exome sequencing (WES) and confirmed the findings through target sequencing. We divulged two previously reported heterozygous missense variations. Notably, WES revealed variants (c.307G>A, rs2229616) in the MC4R and (c.1360-35A>G, rs2258240) in the VCP genes in both families separately. The chromatogram illustrated homozygous unaffected siblings and parents, as well as heterozygous individuals with the disease. Both families segregate with the obesity disorder in an autosomal dominant manner. In Family 1, the change from ‘G’ to ‘A’ in the MC4R gene depicts the mutant allele ‘A’ segregating dominantly from one generation to another. Similarly, the change from ‘A’ to ‘G’ in the VCP gene illustrates the mutant allele ‘G’ segregating dominantly in Family 2.

show abstract

“…Furthermore, deletions in 16p11.2 were associated with genetic vulnerabilities related to both obesity and ASD [90,91]. More recently, in a genetic analysis of very obese children with ASD, Cortes and Wevrick focused on de novo mutations and found that very obese ASD probands had loss of function mutations in DNMT3A and POGZ [92].…”

Section: Geneticsmentioning

confidence: 99%

Risk Factors for Unhealthy Weight Gain and Obesity among Children with Autism Spectrum Disorder

Dhaliwal

Orsso

Richard

et al. 2019

IJMS

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by social and communication deficits and repetitive behaviors. Children with ASD are also at a higher risk for developing overweight or obesity than children with typical development (TD). Childhood obesity has been associated with adverse health outcomes, including insulin resistance, diabetes, heart disease, and certain cancers. Importantly some key factors that play a mediating role in these higher rates of obesity include lifestyle factors and biological influences, as well as secondary comorbidities and medications. This review summarizes current knowledge about behavioral and lifestyle factors that could contribute to unhealthy weight gain in children with ASD, as well as the current state of knowledge of emerging risk factors such as the possible influence of sleep problems, the gut microbiome, endocrine influences and maternal metabolic disorders. We also discuss some of the clinical implications of these risk factors and areas for future research.

show abstract

Genetic analysis of very obese children with autism spectrum disorder

Cited by 9 publications

References 66 publications

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder

Identification of MC4R and VCP Genetic Variants in Two Pakistani Families Showing Symptoms of Diabetes, Hyperphagia, Seizures, and Obesity

Risk Factors for Unhealthy Weight Gain and Obesity among Children with Autism Spectrum Disorder

Contact Info

Product

Resources

About