The diagnostic yield of genetic and metabolic investigations in syndromic and nonsyndromic patients with autism spectrum disorder, global developmental delay, or intellectual disability from a dedicated neurodevelopmental disorders genetics clinic
First‐tier genetic investigations for patients with neurodevelopmental disorders (NDDs) may include chromosomal microarray, Fragile X testing, and screening for inherited metabolic diseases, but most remain undiagnosed upon completion of testing. Here, we report the diagnostic yields of genetic test...
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| Veröffentlicht in: | American journal of medical genetics. Part A 2024-11, Vol.194 (11), p.e63791-n/a |
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| container_title | American journal of medical genetics. Part A |
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| creator | Postma, Julianne K. Harrison, Mary‐Ann Kutcher, Stephen Webster, Richard J. Cloutier, Mireille Bourque, Danielle K. Yu, Andrea C. Carter, Melissa T. |
| description | First‐tier genetic investigations for patients with neurodevelopmental disorders (NDDs) may include chromosomal microarray, Fragile X testing, and screening for inherited metabolic diseases, but most remain undiagnosed upon completion of testing. Here, we report the diagnostic yields of genetic testing for 537 patients with at least one of autism spectrum disorder, global developmental delay, and/or intellectual disability. Patients were assessed in a single neurodevelopmental genetics clinic, and each underwent a standardized history and physical examination. Each patient was characterized as syndromic or nonsyndromic based on clinical features. Our results demonstrate that multigene sequencing (with an NDD gene panel or exome) had a higher diagnostic yield (8%; 95% confidence interval [CI]: 5%, 13%) than chromosomal microarray and Fragile X testing combined (4%; 95% CI: 3%, 7%). Biochemical screening for inherited metabolic diseases had a diagnostic yield of zero. The diagnostic yield of genetic testing was significantly higher for syndromic patients than for nonsyndromic patients (odds ratio [OR] 3.09; 95% CI: 1.46, 6.83) and higher for female patients than for male (OR 3.21; 95% CI: 1.52, 6.82). These results add to the growing evidence supporting a comprehensive genetic evaluation that includes both copy number analysis and sequencing of known NDD genes for patients with NDDs. |
| doi_str_mv | 10.1002/ajmg.a.63791 |
| format | Article |
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Biochemical screening for inherited metabolic diseases had a diagnostic yield of zero. The diagnostic yield of genetic testing was significantly higher for syndromic patients than for nonsyndromic patients (odds ratio [OR] 3.09; 95% CI: 1.46, 6.83) and higher for female patients than for male (OR 3.21; 95% CI: 1.52, 6.82). 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Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Postma, Julianne K.</au><au>Harrison, Mary‐Ann</au><au>Kutcher, Stephen</au><au>Webster, Richard J.</au><au>Cloutier, Mireille</au><au>Bourque, Danielle K.</au><au>Yu, Andrea C.</au><au>Carter, Melissa T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The diagnostic yield of genetic and metabolic investigations in syndromic and nonsyndromic patients with autism spectrum disorder, global developmental delay, or intellectual disability from a dedicated neurodevelopmental disorders genetics clinic</atitle><jtitle>American journal of medical genetics. Part A</jtitle><addtitle>Am J Med Genet A</addtitle><date>2024-11</date><risdate>2024</risdate><volume>194</volume><issue>11</issue><spage>e63791</spage><epage>n/a</epage><pages>e63791-n/a</pages><issn>1552-4825</issn><issn>1552-4833</issn><eissn>1552-4833</eissn><abstract>First‐tier genetic investigations for patients with neurodevelopmental disorders (NDDs) may include chromosomal microarray, Fragile X testing, and screening for inherited metabolic diseases, but most remain undiagnosed upon completion of testing. Here, we report the diagnostic yields of genetic testing for 537 patients with at least one of autism spectrum disorder, global developmental delay, and/or intellectual disability. Patients were assessed in a single neurodevelopmental genetics clinic, and each underwent a standardized history and physical examination. Each patient was characterized as syndromic or nonsyndromic based on clinical features. Our results demonstrate that multigene sequencing (with an NDD gene panel or exome) had a higher diagnostic yield (8%; 95% confidence interval [CI]: 5%, 13%) than chromosomal microarray and Fragile X testing combined (4%; 95% CI: 3%, 7%). Biochemical screening for inherited metabolic diseases had a diagnostic yield of zero. The diagnostic yield of genetic testing was significantly higher for syndromic patients than for nonsyndromic patients (odds ratio [OR] 3.09; 95% CI: 1.46, 6.83) and higher for female patients than for male (OR 3.21; 95% CI: 1.52, 6.82). 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| subjects | Adolescent Adult Autism autism spectrum disorder Autism Spectrum Disorder - diagnosis Autism Spectrum Disorder - genetics Child Child, Preschool chromosomal microarray Copy number Developmental Disabilities - diagnosis Developmental Disabilities - genetics Developmental Disabilities - pathology DNA microarrays exome sequencing Female Genetic analysis Genetic screening Genetic testing Genetic Testing - methods global developmental delay Humans Infant Intellectual disabilities intellectual disability Intellectual Disability - diagnosis Intellectual Disability - genetics Intellectual Disability - pathology Male Metabolic disorders multigene panel Neurodevelopmental disorders Neurodevelopmental Disorders - diagnosis Neurodevelopmental Disorders - genetics Young Adult |
| title | The diagnostic yield of genetic and metabolic investigations in syndromic and nonsyndromic patients with autism spectrum disorder, global developmental delay, or intellectual disability from a dedicated neurodevelopmental disorders genetics clinic |
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