Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank
Objective: 1. To collect historical information and to bank DNA, cells, and tissue from individuals with genetic alterations in the WS/ELN gene region, those with an SVAS -like phenotype and unaffected family members/controls to facilitate future research into the many phenotypes seen in these individuals. 2. Currently, we plan to use the collected samples to identify genetic and environmental factors that contribute to the variability in different phenotypes (vascular and non-vascular) in individuals with WS, SVAS and SVAS-like conditions, individuals with variation in WS genes other than elastin and unaffected family members and controls. For the non-vascular features of WS and SVAS-like conditions for which a specific gene has not been implicated in the disease, we would also like to identify causative genes as well as modifiers. Likewise, by evaluating people with variation in other WS region genes, we can determine what contribution those genes make to the studied phenotypes. Controls will be both used to assess the frequency of genetic features in people without the phenotype in question and to evaluate heritability, penetrance, and expressivity of relevant variants.
Eligibility: People ages 0-85 with either WS, SVAS, and/or an SVAS-like condition, unaffected family members or adult unrelated controls.
Design: This study is not a treatment protocol. This study will consist of: Collection of personal history (questionnaires) and medical record data (relevant physician notes, lab and diagnostic tests and studies) to study the natural history of these conditions, allow stratification of disease severity, and identification of environmental risk factors; Collection of blood, saliva, urine and surgical tissue waste to allow DNA and RNA preparation as well as study of tissues both in situ and through the generation of IPSCs; Expression studies on available tissues (lymphocytes, IPSCs, vascular, skin, other collected tissues) to look for differential regulation of target genes; Direct imaging of tissues (lymphocytes, IPSCs, vascular, skin, other collected tissues); Storage of collected data and specimens for future research; A questionnaire may be sent to participants or parent/guardian or LAR to respond on behalf of participant.
⁃ We will recruit individuals with WS, SVAS or SVAS-like conditions, individuals with variation in WS genes other than ELN and unaffected family members or unrelated controls
⁃ Children or adults participating in this study as part of the WS group must:
• be between the ages of 0 and 85
• have a presumed or confirmed diagnosis of WS (typical or atypical deletions overlapping the WS region are acceptable, as are clinical diagnoses made by a physician familiar with WS) have a parent/guardian available to provide consent and assist in answering medical questions
⁃ Children or adults participating in the study as part of the SVAS/SVAS-like group must:
• be between the ages of 0 and 85
• have clinical features suggestive of SVAS or an SVAS-like condition OR have no clinical features of SVAS or of an SVAS-like condition but have genetic testing results that imply affected status (SVAS has decreased penetrance).
⁃ Have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor (not applicable to adults)
⁃ Children or adults with WS region gene changes (variation affecting one or more WS region genes):
• be between the ages of 0 and 85
• have clinical or research genetic testing that reports gene variation in one or more genes in the WS region (ELN variants alone will be considered in the SVAS category but other changes to the region that include ELN plus other genes may be grouped in this category).
⁃ Have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor or if they have cognitive impairment that would impede their ability to consent on their own behalf.
⁃ Children or adults serving as unaffected family members or adult unrelated controls must:
• family members be between the ages of one month old and 85 years old
• unrelated controls be between the ages 18 and 85 years old
• not carry a diagnosis of WS, SVAS, an SVAS-like condition or a known (at the time of enrollment) WS gene region variant.
• In some cases, an individual may appear to be unaffected, but upon genetic testing may be found to be an asymptomatic carrier for gene variant. If that happens, they will be transferred to the appropriate affected research group.
⁃ The eligible age range for unaffected family members participating in this study includes all family members from one month onwards. This inclusive approach is undertaken to comprehensively grasp the affected status across all family members, avoiding any form of age-based discrimination. Understanding that certain cases may not exhibit phenotypic indications of affected status at a young age, it becomes crucial to gather early health characteristics of individuals who may initially appear unaffected but later manifest disease findings. Participation in research, as previously noted, has a potential to identify people at risk who were previously thought to be healthy.