Clinical Genetic Testing in Autism Spectrum Disorder in a Large Community-Based Population Sample

Moreno‐De‐Luca, Daniel; Kavanaugh, Brian C.; Best, Carrie R.; Sheinkopf, Stephen J.; Phornphutkul, Chanika; Morrow, Eric M.

doi:10.1001/jamapsychiatry.2020.0950

Cited by 37 publications

(20 citation statements)

References 6 publications

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“…One possible explanation was those with higher education and higher income groups were stigmatized and had difficulty accepting their child was born with ASD. However, 24.3% have seen a professional genetic consultant about their child's ASD, which is higher than the report of 20% and 10% of the parents in two studies in the USA (Vande Wydeven et al, 2012;Selkirk et al, 2009) -Luca et al, 2020). However, their sample size was much larger than our study, which may explain this difference.…”

Section: Discussioncontrasting

confidence: 83%

Awareness and perception of medical genetic services among Malaysian parents of autism spectrum disorders children: the lessons to be learned

Amini

Yee

Soh

et al. 2021

AIA

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Purpose Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with uncertain etiology. Evidence shows that genetic testing can explain about 20% of cases. This study aims to assess the level of awareness and perception of medical genetic services among Malaysian parents with ASD children. Design/methodology/approach A cross-sectional survey using an interviewer-administered questionnaire was done among 111 parents of children with ASD from August 2017 to September 2019 in two clinics in Malaysia. Findings A majority of children with ASD (80.20%) were male and diagnosed at the age of 3–4 years old (47.80%). When the autistic child was born, most mothers and fathers were aged 26–30 (40.50%) and 31–35 years old (42.30%), respectively. Another child with ASD in nuclear and extended families was reported for 11.70% and 13.50%, respectively. Only 24.30% have seen a professional genetic consultant, and 19.8% have done genetic testing for affected children. The mean score of awareness of genetic services for ASD was 2.48 ± 3.30. Having medical insurance and another child with ASD in the nuclear family was significantly associated with a higher level of awareness (p = 0.01 and p < 0.001, respectively). Most of the participants have a positive perception of these services. Originality/value Regardless of demographic factors, participants have poor awareness of genetic services for ASD, likely because the primary physician did not recommend it upon diagnosis. Increasing health-care providers’ knowledge about the current potential of genetic testing for ASD and educational campaigns for the public are critical components of using available genetic tests to improve ASD management.

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Section: Discussioncontrasting

confidence: 83%

Awareness and perception of medical genetic services among Malaysian parents of autism spectrum disorders children: the lessons to be learned

Amini

Yee

Soh

et al. 2021

AIA

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“…Indeed, genetic testing in cases of ASD and developmental delay is still vastly underutilized. 51,52 Moving forward, in order to generate robust data from which to draw genotype-phenotype relationships, it will be imperative to address ascertainment bias and expand genetic testing. 53 The expression levels and splicing patterns of genes involved in neurodevelopment can change during the course of development, which can be missed by cross-sectional studies.…”

Section: Scn2a Mutations: a Model For Clinical Development Based On Genotype-phenotype Relationshipsmentioning

confidence: 99%

Harnessing rare variants in neuropsychiatric and neurodevelopment disorders—a Keystone Symposia report

Cable¹,

Purcell

Robinson

et al. 2021

Annals of the New York Academy of Sciences

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Neurodevelopmental neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, have strong genetic risk components, but the underlying mechanisms have proven difficult to decipher. Rare, high-risk variants may offer an opportunity to delineate the biological mechanisms responsible more clearly for more common idiopathic diseases. Indeed, different rare variants can cause the same behavioral phenotype, demonstrating genetic heterogeneity, while the same rare variant can cause different behavioral phenotypes, demonstrating variable expressivity. These observations suggest convergent underlying biological and neurological mechanisms; identification of these mechanisms may ultimately reveal new therapeutic targets. At the 2021 Keystone eSymposium "Neuropsychiatric and Neurodevelopmental Disorders: Harnessing Rare Variants" a panel of experts in the field described significant progress in genomic discovery and human phenotyping and raised several consistent issues, including the need for detailed natural history studies of rare disorders, the challenges in cohort recruitment, and the importance of viewing phenotypes as quantitative traits that are impacted by rare variants.

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“…However, current approaches that determine which patients receive a genetic test are inconsistent and inequitable 6 . For numerous conditions where genetic testing is recommended, the vast majority of patients still do not receive a genetic test 7,8 . Developing a systemized way to identify patients likely to have a rare genetic disease could guide genetic testing decision-making to improve diagnostic outcomes, reduce healthcare costs and burden on patients, and enable opportunities for improved care.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic signatures in clinical data enable systematic identification of patients for genetic testing

Morley

Han

Castro

et al. 2021

Nat Med

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Around five percent of the population is affected by a rare disease, most often due to genetic variation. A genetic test is the quickest path to a diagnosis, yet most suffer through years of diagnostic odyssey before getting a test, if they receive one at all. Identifying patients that are likely to have a genetic disease and therefore need genetic testing is paramount to improving diagnosis and treatment. While there are thousands of previously described genetic diseases with specific phenotypic presentations, a common feature among them is the presence of multiple rare phenotypes which often span organ systems. Here, we hypothesize that these patients can be identified from longitudinal clinical data in the electronic health record (EHR). We used diagnostic information from the EHRs of 2,286 patients that received a chromosomal microarray and 9,144 matched controls to train and test a prediction model. We identified high prediction accuracy (AUROC = 0.97, AUPR = 0.92) in a held-out test sample and in 172,265 hospital patients where cases were defined broadly as interacting with a genetics provider (AUROC = 0.9, AUPR = 0.63). High probabilities (median = 0.97) were associated with 46 patients carrying a known pathogenic copy number variant (CNV) among a subset of 6,445 genotyped patients. Our model identified many more patients needing a genetic test while increasing the proportion having a putative genetic disease compared to the current nonsytematic approach. Taken together, we demonstrate that phenotypic patterns representative of a genetic disease can be captured from EHR data and provide an opportunity to systematize decision making on genetic testing to speed up diagnosis, improve care, and reduce costs.

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Clinical Genetic Testing in Autism Spectrum Disorder in a Large Community-Based Population Sample

Cited by 37 publications

References 6 publications

Awareness and perception of medical genetic services among Malaysian parents of autism spectrum disorders children: the lessons to be learned

Awareness and perception of medical genetic services among Malaysian parents of autism spectrum disorders children: the lessons to be learned

Harnessing rare variants in neuropsychiatric and neurodevelopment disorders—a Keystone Symposia report

Phenotypic signatures in clinical data enable systematic identification of patients for genetic testing

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