Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

A survey of aortic disease biorepository participants’ preferences for return of research genetic results

There is ongoing debate on whether and what research genetic results to return to study participants. To date, no study in this area has focused on aortopathy populations despite known genes that are clinically actionable. Participants (n = 225, 79% male, mean age = 61 years) with an aortopathy were surveyed to assess preferences for receiving research genetic results. Participants were - very- or - extremely likely- to want results for pathogenic variants in aortopathy genes with implications for family members (81%) or that would change medical management (76%). Similarly, participants were - very- or - extremely likely- to want actionable secondary findings related to cancer (75%) or other cardiac diseases (70%). Significantly lower interest was observed for non- actionable findings- pathogenic variants in aortopathy genes that would not change medical management (51%) and variants of uncertain significance (38%) (p 63%) were accepting of any means of return; however, a substantial minority (18%- 38%) deemed certain technological means unacceptable (e.g., patient portal). Over 90% of participants reported that a range of health professionals, including cardiovascular specialists, genetics specialists, and primary care providers, were acceptable to return results. Participants with aortopathies are highly interested in research genetic results perceived to be medically actionable for themselves or family members. Participants are accepting of a variety of means for returning results. Findings suggest that research participants should be asked what results are preferred at time of informed consent and that genetic counseling may clarify implications of results that are not personally medically actionable.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/1/jgc41341_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/2/jgc41341-sup-0004-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/3/jgc41341.pd

A survey of aortic disease biorepository participants- preferences for return of research genetic results

There is ongoing debate on whether and what research genetic results to return to study participants. To date, no study in this area has focused on aortopathy populations despite known genes that are clinically actionable. Participants (n = 225, 79% male, mean age = 61 years) with an aortopathy were surveyed to assess preferences for receiving research genetic results. Participants were - very- or - extremely likely- to want results for pathogenic variants in aortopathy genes with implications for family members (81%) or that would change medical management (76%). Similarly, participants were - very- or - extremely likely- to want actionable secondary findings related to cancer (75%) or other cardiac diseases (70%). Significantly lower interest was observed for non- actionable findings- pathogenic variants in aortopathy genes that would not change medical management (51%) and variants of uncertain significance (38%) (p 63%) were accepting of any means of return; however, a substantial minority (18%- 38%) deemed certain technological means unacceptable (e.g., patient portal). Over 90% of participants reported that a range of health professionals, including cardiovascular specialists, genetics specialists, and primary care providers, were acceptable to return results. Participants with aortopathies are highly interested in research genetic results perceived to be medically actionable for themselves or family members. Participants are accepting of a variety of means for returning results. Findings suggest that research participants should be asked what results are preferred at time of informed consent and that genetic counseling may clarify implications of results that are not personally medically actionable.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/1/jgc41341_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/2/jgc41341-sup-0004-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/3/jgc41341.pd

Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

Abstract: Purpose: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. Methods: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. Results: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15–20%). Conclusion: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs

Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders.

PURPOSE: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. METHODS: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. RESULTS: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15-20%). CONCLUSION: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs

Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders.

PURPOSE: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. METHODS: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. RESULTS: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15-20%). CONCLUSION: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs