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. 2022 Jun 28;14(1):40.
doi: 10.1186/s11689-022-09449-7.

Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications

Jennifer M Bain  1 , LeeAnne Green Snyder  2 , Katherine L Helbig  3 , Dominique D Cooper  4 , Wendy K Chung  2   5 , Kimberly Goodspeed  6
Affiliations

Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications

Jennifer M Bain et al. J Neurodev Disord. .

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.

Keywords: Autism; Epilepsy; Genetic; Hypotonia; Intellectual disability; Movement disorder; Neurodevelopmental disorder; SLC6A1.

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Conflict of interest statement

KG receives salary support for research from Taysha Gene Therapies. JB receives salary support for research from Simons Searchlight. The other authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
The Vineland Adaptive Behavior Scale (VABS) is a standardized assessment of adaptive behavior skills across four domains: Communication, Motor, Daily Living Skills, and Socialization. The chronological age at the time of evaluation (years) is plotted against the estimated age-equivalent of the following subdomains: expressive language skills, personal daily living skills, interpersonal relationship skills, and fine motor skills. The motor domains of the VABS have a ceiling of approximately 8 years. The gray lines represent the cross-section of the chronological age and age-equivalent at 5 years for expressive language skills, personal daily living skills, and interpersonal relationship skills, and 4 years for fine motor skills
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