Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications
Abstract Background SLC6A1-related disorder is a recently identified, rare, genetic neurodevelopmental disorder that is associated with loss-of-function variants in SLC6A1. This gene encodes GABA transporter type I that is responsible for re-uptake of GABA from the synapse into the pre-synaptic term...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11689-022-09449-7 |
| _version_ | 1811328838086426624 |
|---|---|
| author | Jennifer M. Bain LeeAnne Green Snyder Katherine L. Helbig Dominique D. Cooper Wendy K. Chung Kimberly Goodspeed |
| author_facet | Jennifer M. Bain LeeAnne Green Snyder Katherine L. Helbig Dominique D. Cooper Wendy K. Chung Kimberly Goodspeed |
| author_sort | Jennifer M. Bain |
| collection | DOAJ |
| description | Abstract Background SLC6A1-related disorder is a recently identified, rare, genetic neurodevelopmental disorder that is associated with loss-of-function variants in SLC6A1. This gene encodes GABA transporter type I that is responsible for re-uptake of GABA from the synapse into the pre-synaptic terminal or circulating neuroglia. Based upon retrospective review of published cases and available research databases including Epi25 collective and SLC6A1 Connect patient database, the phenotypic spectrum is broad and includes developmental delay, epilepsy, and autism or autistic traits. SLC6A1 is one of the genes included in the Simons Searchlight registry, which includes standardized data collection across genetically identified neurodevelopmental conditions. Methods In this study, we compare parent-report measures of phenotypic features in the Simons Searchlight registry to previously published, provider-reported cases to assess if parent-report measures are consistent with what has been reported in the literature. Results There were 116 participants in the provider-reported dataset compared to 43 individuals in the caregiver-reported dataset. Carriers in Searchlight had 83 unique pathogenic or likely pathogenic variants in SLC6A1, which were predominantly missense or nonsense variants. There was no significant difference between groups for the prevalence of developmental delay, ASD, or ADHD. Caregivers more often reported hypotonia, while epilepsy was slightly more frequently reported by providers. Conclusions We propose that standardized parent-report data collection methods are consistent with provider reports on many core features of SLC6A1-related disorder. The availability of patient registries and standardized natural history studies may fill an important need in clinical trial readiness programs, with larger sample sizes than smaller published case series. |
| first_indexed | 2024-04-13T15:32:58Z |
| format | Article |
| id | doaj.art-58ab5c3be7524a05999d9217d9d8fe04 |
| institution | Directory Open Access Journal |
| issn | 1866-1947 1866-1955 |
| language | English |
| last_indexed | 2024-04-13T15:32:58Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-58ab5c3be7524a05999d9217d9d8fe042022-12-22T02:41:20ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552022-06-011411810.1186/s11689-022-09449-7Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based PublicationsJennifer M. Bain0LeeAnne Green Snyder1Katherine L. Helbig2Dominique D. Cooper3Wendy K. Chung4Kimberly Goodspeed5Department of Neurology, Division of Child Neurology, Columbia University Irving Medical CenterSimons FoundationDepartment of Pediatrics, Division of Neurology and Epilepsy NeuroGenetics Initiative, Children’s Hospital of PhiladelphiaUniversity of Texas Southwestern Medical CenterSimons FoundationDepartment of Pediatrics, Division of Neurology, University of Texas Southwestern Medical CenterAbstract Background SLC6A1-related disorder is a recently identified, rare, genetic neurodevelopmental disorder that is associated with loss-of-function variants in SLC6A1. This gene encodes GABA transporter type I that is responsible for re-uptake of GABA from the synapse into the pre-synaptic terminal or circulating neuroglia. Based upon retrospective review of published cases and available research databases including Epi25 collective and SLC6A1 Connect patient database, the phenotypic spectrum is broad and includes developmental delay, epilepsy, and autism or autistic traits. SLC6A1 is one of the genes included in the Simons Searchlight registry, which includes standardized data collection across genetically identified neurodevelopmental conditions. Methods In this study, we compare parent-report measures of phenotypic features in the Simons Searchlight registry to previously published, provider-reported cases to assess if parent-report measures are consistent with what has been reported in the literature. Results There were 116 participants in the provider-reported dataset compared to 43 individuals in the caregiver-reported dataset. Carriers in Searchlight had 83 unique pathogenic or likely pathogenic variants in SLC6A1, which were predominantly missense or nonsense variants. There was no significant difference between groups for the prevalence of developmental delay, ASD, or ADHD. Caregivers more often reported hypotonia, while epilepsy was slightly more frequently reported by providers. Conclusions We propose that standardized parent-report data collection methods are consistent with provider reports on many core features of SLC6A1-related disorder. The availability of patient registries and standardized natural history studies may fill an important need in clinical trial readiness programs, with larger sample sizes than smaller published case series.https://doi.org/10.1186/s11689-022-09449-7SLC6A1Neurodevelopmental disorderIntellectual disabilityGeneticEpilepsyAutism |
| spellingShingle | Jennifer M. Bain LeeAnne Green Snyder Katherine L. Helbig Dominique D. Cooper Wendy K. Chung Kimberly Goodspeed Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications Journal of Neurodevelopmental Disorders SLC6A1 Neurodevelopmental disorder Intellectual disability Genetic Epilepsy Autism |
| title | Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications |
| title_full | Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications |
| title_fullStr | Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications |
| title_full_unstemmed | Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications |
| title_short | Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications |
| title_sort | consistency of parent report slc6a1 data in simons searchlight with provider based publications |
| topic | SLC6A1 Neurodevelopmental disorder Intellectual disability Genetic Epilepsy Autism |
| url | https://doi.org/10.1186/s11689-022-09449-7 |
| work_keys_str_mv | AT jennifermbain consistencyofparentreportslc6a1datainsimonssearchlightwithproviderbasedpublications AT leeannegreensnyder consistencyofparentreportslc6a1datainsimonssearchlightwithproviderbasedpublications AT katherinelhelbig consistencyofparentreportslc6a1datainsimonssearchlightwithproviderbasedpublications AT dominiquedcooper consistencyofparentreportslc6a1datainsimonssearchlightwithproviderbasedpublications AT wendykchung consistencyofparentreportslc6a1datainsimonssearchlightwithproviderbasedpublications AT kimberlygoodspeed consistencyofparentreportslc6a1datainsimonssearchlightwithproviderbasedpublications |