Automated extraction of functional biomarkers of verbal and ambulatory ability from multi-institutional clinical notes using large language models / Levi KASTER in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Automated extraction of functional biomarkers of verbal and ambulatory ability from multi-institutional clinical notes using large language models Type de document : texte imprimé Auteurs : Levi KASTER, Auteur ; Ethan HILLIS, Auteur ; Inez Y. OH, Auteur ; Bhooma R. ARAVAMUTHAN, Auteur ; Virginia C. LANZOTTI, Auteur ; Casey R. VICKSTROM, Auteur ; BRAIN GENE REGISTRY CONSORTIUM, Auteur ; Christina A. GURNETT, Auteur ; Philip R.O. PAYNE, Auteur ; Aditi GUPTA, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Child  Child, Preschool  Female  Humans  Male  Young Adult  Biomarkers  Cerebral Palsy/physiopathology/diagnosis  Developmental Disabilities/physiopathology/diagnosis  Electronic Health Records  Intellectual Disability/physiopathology/diagnosis  Large Language Models  Natural Language Processing  Registries  Electronic health records  Functional biomarkers  Large language models  Neurodevelopmental disorders  recruited specifically for this study. This work constitutes secondary use of  data approved by the Washington University in St. Louis IRB (protocols #202010013  [Brain Gene Registry cohort] and #202309003 [cerebral palsy cohort]). Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical notes, which are rich in longitudinal data, may provide a low-burden pipeline for extracting functional biomarkers efficiently and accurately. METHODS: Data from the multi-institutional National Brain Gene Registry (BGR) and a CP clinic cohort were utilized, comprising 3,245 notes from 125 individuals and 5,462 clinical notes from 260 individuals, respectively. Employing three LLMs-GPT-3.5 Turbo, GPT-4 Turbo, and GPT-4 Omni-we provided the models with a clinical note and utilized a detailed conversational format to prompt the models to answer: "Does the individual use any words?" and "Can the individual walk without aid?" These responses were evaluated against ground-truth abilities, which were established using neurobehavioral assessments collected for each dataset. RESULTS: LLM pipelines demonstrated high accuracy (weighted-F1 scores > .90) in predicting ambulatory ability for both cohorts, likely due to the consistent use of Gross Motor Functional Classification System (GMFCS) as a consistent ground-truth standard. However, verbal ability predictions were more accurate in the BGR cohort, likely due to higher adherence between the prompt and ground-truth assessment questions. While LLMs can be computationally expensive, analysis of our protocol affirmed the cost effectiveness when applied to select notes from the EHR. CONCLUSIONS: LLMs are effective at extracting functional biomarkers from EHR data and broadly generalizable across variable note-taking practices and institutions. Individual verbal and ambulatory ability were accurately extracted, supporting the method's ability to streamline workflows by offering automated, efficient data extraction for patient care and research. Future studies are needed to extend this methodology to additional populations and to demonstrate more granular functional data classification. En ligne : https://dx.doi.org/10.1186/s11689-025-09612-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Automated extraction of functional biomarkers of verbal and ambulatory ability from multi-institutional clinical notes using large language models [texte imprimé] / Levi KASTER, Auteur ; Ethan HILLIS, Auteur ; Inez Y. OH, Auteur ; Bhooma R. ARAVAMUTHAN, Auteur ; Virginia C. LANZOTTI, Auteur ; Casey R. VICKSTROM, Auteur ; BRAIN GENE REGISTRY CONSORTIUM, Auteur ; Christina A. GURNETT, Auteur ; Philip R.O. PAYNE, Auteur ; Aditi GUPTA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Adolescent  Adult  Child  Child, Preschool  Female  Humans  Male  Young Adult  Biomarkers  Cerebral Palsy/physiopathology/diagnosis  Developmental Disabilities/physiopathology/diagnosis  Electronic Health Records  Intellectual Disability/physiopathology/diagnosis  Large Language Models  Natural Language Processing  Registries  Electronic health records  Functional biomarkers  Large language models  Neurodevelopmental disorders  recruited specifically for this study. This work constitutes secondary use of  data approved by the Washington University in St. Louis IRB (protocols #202010013  [Brain Gene Registry cohort] and #202309003 [cerebral palsy cohort]). Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical notes, which are rich in longitudinal data, may provide a low-burden pipeline for extracting functional biomarkers efficiently and accurately. METHODS: Data from the multi-institutional National Brain Gene Registry (BGR) and a CP clinic cohort were utilized, comprising 3,245 notes from 125 individuals and 5,462 clinical notes from 260 individuals, respectively. Employing three LLMs-GPT-3.5 Turbo, GPT-4 Turbo, and GPT-4 Omni-we provided the models with a clinical note and utilized a detailed conversational format to prompt the models to answer: "Does the individual use any words?" and "Can the individual walk without aid?" These responses were evaluated against ground-truth abilities, which were established using neurobehavioral assessments collected for each dataset. RESULTS: LLM pipelines demonstrated high accuracy (weighted-F1 scores > .90) in predicting ambulatory ability for both cohorts, likely due to the consistent use of Gross Motor Functional Classification System (GMFCS) as a consistent ground-truth standard. However, verbal ability predictions were more accurate in the BGR cohort, likely due to higher adherence between the prompt and ground-truth assessment questions. While LLMs can be computationally expensive, analysis of our protocol affirmed the cost effectiveness when applied to select notes from the EHR. CONCLUSIONS: LLMs are effective at extracting functional biomarkers from EHR data and broadly generalizable across variable note-taking practices and institutions. Individual verbal and ambulatory ability were accurately extracted, supporting the method's ability to streamline workflows by offering automated, efficient data extraction for patient care and research. Future studies are needed to extend this methodology to additional populations and to demonstrate more granular functional data classification. En ligne : https://dx.doi.org/10.1186/s11689-025-09612-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk / Natasha MARRUS in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk Type de document : texte imprimé Auteurs : Natasha MARRUS, Auteur ; Tychele N. TURNER, Auteur ; Elizabeth FORSEN, Auteur ; Drew BOLSTER, Auteur ; Alison MARVIN, Auteur ; Andrew WHITEHOUSE, Auteur ; Laura KLINGER, Auteur ; Christina A. GURNETT, Auteur ; J.N. CONSTANTINO, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics  Autistic Disorder/epidemiology/genetics  Genetic Counseling  Humans  Parents  Prospective Studies  Early detection  Family studies  Personalized medicine  Reproductive health planning  for the Social Responsiveness Scale. Index. décimale : PER Périodiques Résumé : BACKGROUND: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3-5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling. METHODS: We assembled what is to our knowledge the largest collection of data on the ability of four measurable characteristics of unaffected prospective parents to specify risk for autism among their offspring: (1) sub clinical autistic trait burden, (2) parental history of a sibling with ASD, (3) transmitted autosomal molecular genetic abnormalities, and (4) parental age. Leveraging phenotypic and genetic data in curated family cohorts, we evaluate the respective associations between these factors and child outcome when autism is present in the family in the parental generation. RESULTS: All four characteristics were associated with elevation in offspring risk; however, the magnitude of their predictive power-with the exception of isolated rare inherited pathogenic variants -does not yet reach a threshold that would typically be considered actionable for reproductive decision-making. CONCLUSIONS: Individual specification of risk to offspring of adults in ASD-affected families is not straightforwardly improved by ascertainment of parental phenotype, and it is not yet clear whether genomic screening of prospective parents in families affected by idiopathic ASD is warranted as a clinical standard. Systematic screening of affected family members for heritable pathogenic variants, including rare sex-linked mutations, will identify a subset of families with substantially elevated transmission risk. Polygenic risk scores are only weakly predictive at this time but steadily improving and ultimately may enable more robust prediction either singly or when combined with the risk variables examined in this study. En ligne : https://dx.doi.org/10.1186/s11689-021-09389-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk [texte imprimé] / Natasha MARRUS, Auteur ; Tychele N. TURNER, Auteur ; Elizabeth FORSEN, Auteur ; Drew BOLSTER, Auteur ; Alison MARVIN, Auteur ; Andrew WHITEHOUSE, Auteur ; Laura KLINGER, Auteur ; Christina A. GURNETT, Auteur ; J.N. CONSTANTINO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics  Autistic Disorder/epidemiology/genetics  Genetic Counseling  Humans  Parents  Prospective Studies  Early detection  Family studies  Personalized medicine  Reproductive health planning  for the Social Responsiveness Scale. Index. décimale : PER Périodiques Résumé : BACKGROUND: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3-5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling. METHODS: We assembled what is to our knowledge the largest collection of data on the ability of four measurable characteristics of unaffected prospective parents to specify risk for autism among their offspring: (1) sub clinical autistic trait burden, (2) parental history of a sibling with ASD, (3) transmitted autosomal molecular genetic abnormalities, and (4) parental age. Leveraging phenotypic and genetic data in curated family cohorts, we evaluate the respective associations between these factors and child outcome when autism is present in the family in the parental generation. RESULTS: All four characteristics were associated with elevation in offspring risk; however, the magnitude of their predictive power-with the exception of isolated rare inherited pathogenic variants -does not yet reach a threshold that would typically be considered actionable for reproductive decision-making. CONCLUSIONS: Individual specification of risk to offspring of adults in ASD-affected families is not straightforwardly improved by ascertainment of parental phenotype, and it is not yet clear whether genomic screening of prospective parents in families affected by idiopathic ASD is warranted as a clinical standard. Systematic screening of affected family members for heritable pathogenic variants, including rare sex-linked mutations, will identify a subset of families with substantially elevated transmission risk. Polygenic risk scores are only weakly predictive at this time but steadily improving and ultimately may enable more robust prediction either singly or when combined with the risk variables examined in this study. En ligne : https://dx.doi.org/10.1186/s11689-021-09389-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

SARS-CoV-2 screening testing in schools for children with intellectual and developmental disabilities / Michael R. SHERBY in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : SARS-CoV-2 screening testing in schools for children with intellectual and developmental disabilities Type de document : texte imprimé Auteurs : Michael R. SHERBY, Auteur ; Tyler J. WALSH, Auteur ; Albert M. LAI, Auteur ; Julie A. NEIDICH, Auteur ; Joyce E. BALLS-BERRY, Auteur ; Stephanie M. MORRIS, Auteur ; Richard HEAD, Auteur ; Christopher G. PRENER, Auteur ; Jason G. NEWLAND, Auteur ; Christina A. GURNETT, Auteur ; COMPASS-T STUDY GROUP, Auteur Langues : Anglais (eng) Mots-clés : covid-19  Child  Developmental Disabilities/diagnosis/epidemiology  Humans  Pandemics  SARS-CoV-2  Schools  Covid-19  COVID-19 School tests  Children with IDD  Intellectual and developmental disabilities  SARS-CoV-2 testing Index. décimale : PER Périodiques Résumé : BACKGROUND: Transmission of SARS-CoV-2 in schools primarily for typically developing children is rare. However, less is known about transmission in schools for children with intellectual and developmental disabilities (IDD), who are often unable to mask or maintain social distancing. The objectives of this study were to determine SARS-CoV-2 positivity and in-school transmission rates using weekly screening tests for school staff and students and describe the concurrent deployment of mitigation strategies in six schools for children with IDD. METHODS: From November 23, 2020, to May, 28, 2021, weekly voluntary screening for SARS-CoV-2 with a high sensitivity molecular-based saliva test was offered to school staff and students. Weekly positivity rates were determined and compared to local healthcare system and undergraduate student screening data. School-based transmission was assessed among participants quarantined for in-school exposure. School administrators completed a standardized survey to assess school mitigation strategies. RESULTS: A total of 59 students and 416 staff participated. An average of 304 school staff and students were tested per week. Of 7289 tests performed, 21 (0.29%) new SARS-CoV-2 positive cases were identified. The highest weekly positivity rate was 1.2% (n = 4) across all schools, which was less than community positivity rates. Two cases of in-school transmission were identified, each among staff, representing 2% (2/103) of participants quarantined for in-school exposure. Mitigation strategies included higher than expected student mask compliance, reduced room capacity, and phased reopening. CONCLUSIONS: During 24 weeks that included the peak of the COVID-19 pandemic in winter 2020-21, we found lower rates of SARS-CoV-2 screening test positivity among staff and students of six schools for children with IDD compared to community rates. In-school transmission of SARS-CoV-2 was low among those quarantined for in-school exposure. However, the impact of the emerging SARS-CoV-2 Delta variant on the effectiveness of these proven mitigation strategies remains unknown. TRIAL REGISTRATION: Prior to enrollment, this study was registered at ClinicalTrials.gov on September 25, 2020, identifier NCT04565509 , titled Supporting the Health and Well-being of Children with Intellectual and Developmental Disability During COVID-19 Pandemic. En ligne : https://dx.doi.org/10.1186/s11689-021-09376-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] SARS-CoV-2 screening testing in schools for children with intellectual and developmental disabilities [texte imprimé] / Michael R. SHERBY, Auteur ; Tyler J. WALSH, Auteur ; Albert M. LAI, Auteur ; Julie A. NEIDICH, Auteur ; Joyce E. BALLS-BERRY, Auteur ; Stephanie M. MORRIS, Auteur ; Richard HEAD, Auteur ; Christopher G. PRENER, Auteur ; Jason G. NEWLAND, Auteur ; Christina A. GURNETT, Auteur ; COMPASS-T STUDY GROUP, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : covid-19  Child  Developmental Disabilities/diagnosis/epidemiology  Humans  Pandemics  SARS-CoV-2  Schools  Covid-19  COVID-19 School tests  Children with IDD  Intellectual and developmental disabilities  SARS-CoV-2 testing Index. décimale : PER Périodiques Résumé : BACKGROUND: Transmission of SARS-CoV-2 in schools primarily for typically developing children is rare. However, less is known about transmission in schools for children with intellectual and developmental disabilities (IDD), who are often unable to mask or maintain social distancing. The objectives of this study were to determine SARS-CoV-2 positivity and in-school transmission rates using weekly screening tests for school staff and students and describe the concurrent deployment of mitigation strategies in six schools for children with IDD. METHODS: From November 23, 2020, to May, 28, 2021, weekly voluntary screening for SARS-CoV-2 with a high sensitivity molecular-based saliva test was offered to school staff and students. Weekly positivity rates were determined and compared to local healthcare system and undergraduate student screening data. School-based transmission was assessed among participants quarantined for in-school exposure. School administrators completed a standardized survey to assess school mitigation strategies. RESULTS: A total of 59 students and 416 staff participated. An average of 304 school staff and students were tested per week. Of 7289 tests performed, 21 (0.29%) new SARS-CoV-2 positive cases were identified. The highest weekly positivity rate was 1.2% (n = 4) across all schools, which was less than community positivity rates. Two cases of in-school transmission were identified, each among staff, representing 2% (2/103) of participants quarantined for in-school exposure. Mitigation strategies included higher than expected student mask compliance, reduced room capacity, and phased reopening. CONCLUSIONS: During 24 weeks that included the peak of the COVID-19 pandemic in winter 2020-21, we found lower rates of SARS-CoV-2 screening test positivity among staff and students of six schools for children with IDD compared to community rates. In-school transmission of SARS-CoV-2 was low among those quarantined for in-school exposure. However, the impact of the emerging SARS-CoV-2 Delta variant on the effectiveness of these proven mitigation strategies remains unknown. TRIAL REGISTRATION: Prior to enrollment, this study was registered at ClinicalTrials.gov on September 25, 2020, identifier NCT04565509 , titled Supporting the Health and Well-being of Children with Intellectual and Developmental Disability During COVID-19 Pandemic. En ligne : https://dx.doi.org/10.1186/s11689-021-09376-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The Brain Gene Registry: a data snapshot / Dustin BALDRIDGE in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : The Brain Gene Registry: a data snapshot Type de document : texte imprimé Auteurs : Dustin BALDRIDGE, Auteur ; Levi KASTER, Auteur ; Catherine SANCIMINO, Auteur ; Siddharth SRIVASTAVA, Auteur ; Sophie MOLHOLM, Auteur ; Aditi GUPTA, Auteur ; Inez OH, Auteur ; Virginia LANZOTTI, Auteur ; Daleep GREWAL, Auteur ; Erin Rooney RIGGS, Auteur ; Juliann M. SAVATT, Auteur ; Rachel HAUCK, Auteur ; Abigail SVEDEN, Auteur ; BRAIN GENE REGISTRY CONSORTIUM, Auteur ; John N. CONSTANTINO, Auteur ; Joseph PIVEN, Auteur ; Christina A. GURNETT, Auteur ; Maya CHOPRA, Auteur ; Heather HAZLETT, Auteur ; Philip R.O. PAYNE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Autism Spectrum Disorder/genetics  Autistic Disorder  Neurodevelopmental Disorders  Intellectual Disability  Brain  Registries  Methyltransferases  Brain gene registry  Electronic health records  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource's (ClinGen's) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen's BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-024-09530-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] The Brain Gene Registry: a data snapshot [texte imprimé] / Dustin BALDRIDGE, Auteur ; Levi KASTER, Auteur ; Catherine SANCIMINO, Auteur ; Siddharth SRIVASTAVA, Auteur ; Sophie MOLHOLM, Auteur ; Aditi GUPTA, Auteur ; Inez OH, Auteur ; Virginia LANZOTTI, Auteur ; Daleep GREWAL, Auteur ; Erin Rooney RIGGS, Auteur ; Juliann M. SAVATT, Auteur ; Rachel HAUCK, Auteur ; Abigail SVEDEN, Auteur ; BRAIN GENE REGISTRY CONSORTIUM, Auteur ; John N. CONSTANTINO, Auteur ; Joseph PIVEN, Auteur ; Christina A. GURNETT, Auteur ; Maya CHOPRA, Auteur ; Heather HAZLETT, Auteur ; Philip R.O. PAYNE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Male  Female  Autism Spectrum Disorder/genetics  Autistic Disorder  Neurodevelopmental Disorders  Intellectual Disability  Brain  Registries  Methyltransferases  Brain gene registry  Electronic health records  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource's (ClinGen's) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen's BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-024-09530-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

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