This is a competitive renewal application from an inter-institutional group of investigators with long-standing interest in Angelman syndrome (AS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS) to continue a Rare Diseases Clinical Research Center (RDCRC) within the Rare Diseases Clinical Research Network (RDCRN). The Center will focus on these three disorders based on the expectation that the near-term potential for meaningful therapy is strong.
The specific aims for RTT will be 1) to establish phenotype/genotype correlations over a broad spectrum of Rett phenotypes, 2) to perform longitudinal studies on an extensive population of individuals with Rett, and 3) to extend the survival study on a broad spectrum of Rett individuals. Recent results from studies in animal models provide a basis for clinical trials in the next 5 years. In addition, evidence emerging from the proposed pilot study on sleep dysfunction in the three disorders should provide the basis for a clinical trial on sleep in RTT. The RTT component sites include UAB, Children's Hospital Boston, Greenwood Genetic Center, and Baylor College of Medicine. GCRCs will be utlized in Birmingham, Boston, and Houston. The travel clinics in Oakland, Chicago, New Brunswick, and Miami will continue to provide geographic diversity for study participants. The Center is expected to function synergistically with the Intellectual and Developmental Disability Center-IDDRC (formerly the MRRC) at UAB, Children's Hospital Boston, and Baylor. An extensive training program is proposed for stimulating the entry of new investigators into clinical research on rare diseases (funded by IRSF and PWSA). The RTT sites will have active affiliation with the International Rett Syndrome Foundation (IRSF). A website for this RDCRC is available at www.circ.uab.edu. This site will be amplified to include a wide range of information on all three disorders.

Public Health Relevance

Effective treatment of Angelman syndrome (AS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS) requires understanding their natural history through longitudinal assessments. We believe more strongly than in the initial proposal that near-term potential for therapy in these disorders is promising. Thus, understanding their common clinical issues disorders (such as nutrition, seizures, sleep and behavior) and the most effective interventions for them are highly relevant.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD061222-09
Application #
8381948
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
9
Fiscal Year
2012
Total Cost
$36,813
Indirect Cost
$3,311
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Sajan, Samin A; Jhangiani, Shalini N; Muzny, Donna M et al. (2017) Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2. Genet Med 19:13-19
Dy, Marisela E; Waugh, Jeff L; Sharma, Nutan et al. (2017) Defining Hand Stereotypies in Rett Syndrome: A Movement Disorders Perspective. Pediatr Neurol 75:91-95
Killian, John T; Lane, Jane B; Lee, Hye-Seung et al. (2017) Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors. Pediatr Neurol 70:20-25
Tarquinio, Daniel C; Hou, Wei; Berg, Anne et al. (2017) Longitudinal course of epilepsy in Rett syndrome and related disorders. Brain 140:306-318
Tan, Wen-Hann; Bird, Lynne M; Sadhwani, Anjali et al. (2017) A randomized controlled trial of levodopa in patients with Angelman syndrome. Am J Med Genet A :
Lane, Jane B; Salter, Amber R; Jones, Nancy E et al. (2017) Assessment of Caregiver Inventory for Rett Syndrome. J Autism Dev Disord 47:1102-1112
Merkel, Peter A; Manion, Michele; Gopal-Srivastava, Rashmi et al. (2016) The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis 11:66
Percy, Alan K (2016) Progress in Rett Syndrome: from discovery to clinical trials. Wien Med Wochenschr 166:325-32
Shivers, Carolyn M; Leonczyk, Caroline L; Dykens, Elisabeth M (2016) Life Satisfaction Among Mothers of Individuals with Prader-Willi Syndrome. J Autism Dev Disord 46:2126-37
Killian Jr, John T; Lane, Jane B; Lee, Hye-Seung et al. (2016) Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors. Pediatr Neurol 58:67-74

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