Data has been collected mainly from direct patient/geneticist/neurologist contact and rare disease survey responders via the KCNMA1 International Advocacy Foundation (https://www.kciaf.org/registry). The KCIAF link contains instructions to initiate the standarized survey through the partner organization website, Sanford Coordination of Rare Diseases (CORDs) (https://research.sanfordhealth.org/rare-disease-registry). Patients and families will click on ‘Enroll Now’ to begin the consent process and obtain the survey questionnaire for KCNMA1. All survey responses are de-identified for Non-Human Subject Research (NHSR). The same information can be submitted to both Human Disease Genes website and the KCIAF/CORDs survey.
To date, approximately 103 patients have been identified, defined as a KCNMA1 genetic variant (mutation) associated with 1-4 core features of the disorder. Still, more investigation is required to understand the full clinical spectrum of KCNMA1 variants. Data ascertainment bias, patient variability, lack of inheritance, diagnostic uncertainty, and the age range of participants has contributed heterogeneity of available data. Causality has only been formally established for two gain-of-function variants, based on pedigree transmission and replication of patient phenotypes in animal models.
Providing genotype-phenotype information via the Human Disease Genes website, or the KCIAF/CORDs survey, is used to develop mechanistic hypotheses concerning the origins and potential treatments for the disorder. Broad aims of future research include:
• Identifying and characterizing patient phenotypes associated with KCNMA1 variants
• Investigating potential therapeutic management therapies and precision medicine
• Understanding the neurological basis for PNKD3
Clinicians and families can aid in the research aims by submitting data directly into the database under the “Upload Clinical Information” tab after patient consent has been obtained.
KCNMA1