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Research

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SAS REGISTRY
clinical research
basic & translational research

SAS REGISTRY

Since 2016, Dr. Yuri Zarate has led a genetic registry focused on studying SATB2-associated syndrome (SAS).

Since enrollment of the first individual with SAS in March of 2016, 149 individuals from over 15 different countries have completed registry data collection as of May of 2019.

 

 

Data generated from the SAS registry has greatly increased our knowledge about this condition with several manuscripts produced and more planned (see Clinical Research).1,2,3,4,5  The SAS registry also offers a large compilation of curated molecular data.

 

 

WHAT IS INVOLVED

There are a few things that need to be completed to be a part of this study registry. The parents or legal guardians perform these steps as necessary.

To learn more about the process:

SAS Registry & Info sheet pdf

 

References: 1. Zarate YA, et al. Hum Mutat. 2019; PMID: 31021519; 2. Scott et al. Clin Oral Investig. 2018; PMID: 30315422. 3. Scott et al. Spec Care Dentist. 2019; PMID: 30648748. 4. Zarate YA, et al. Clin Genet. 2018; PMID: 28787087; 5. Zarate YA, et al. Am J Med Genet A. 2018; PMID: 29436146.

CLINICAL RESEARCH

Arkansas Children’s Hospital SAS team has evaluated dozens of individuals with this rare condition. Understanding the full spectrum of clinical manifestations and neurobehavioral implications of SAS is paramount to develop best care guidelines and anticipate potential complications.

 

 

Ongoing and upcoming clinical research efforts by the Arkansas Children’s Hospital SAS team through ongoing evaluation of individuals affected with SAS and evaluations and SAS registry data, include the following:

  • SPEECH: To characterize the impact SAS has on expressive and receptive language skills and to provide better guidance to families and providers on best interventions.
  • BEHAVIOR: To develop a neurocognitive profile for SAS that allows families and providers to plan ahead and develop optimal management practices.
  • DENTAL AND ORAL PHENOTYPE: To continue to expand our knowledge on the different dental problems and other manifestation of the oral cavity.
  • BONE HEALTH: To explore markers of bone health in SAS that can provide further insight into the pathogenesis of the disease and offer management alternatives.
  • SEIZURES: To get a deeper understanding of the frequency of epilepsy, seizure semiology and risk factors.
  • GROWTH: To analyze growth patterns in SAS and how they correlate with underlying genetic mechanism of disease.

 

References: 1. Zarate YA, et al. Hum Mutat. 2019; PMID: 31021519; 2. Scott et al. Clin Oral Investig. 2018; PMID: 30315422. 3. Scott et al. Spec Care Dentist. 2019; PMID: 30648748. 4. Zarate YA, et al. Clin Genet. 2018; PMID: 28787087; 5. Zarate YA, et al. Am J Med Genet A. 2018; PMID: 29436146.

BASIC AND TRANSLATIONAL RESEARCH

Arkansas Children’s Hospital SAS team and in collaboration with Dr. Jennifer Fish, Assistant Professor at the University of Massachusetts Lowell, is working on several fronts at the Basic and Translational science side to enhance our understanding of SAS. The long term goal of our combined work is to find interventions that are specific for this condition.

 

 

Ongoing and upcoming Basic and Translational Research efforts include the following:

  • PROTEOMIC AND TRANSCRIPTOME ANALYSIS: To develop specific proteomic and transcriptome profiles in blood samples from individuals with SAS.

Venn plot analysis of genes expressed in blood from 5 different individuals with SAS with truncating pathogenic variants

  • METABOLIC AND CHEMICAL SENSITIVITY PHENOTYPES: To quantitatively measure cellular phenotypes through hundreds of chemical reactions on SAS patient-derived cell lines.

Biolog kinetic curves from individuals with SAS.

  • MECHANISMS OF CRANIOFACIAL AND BONE DEVELOPMENT IN MICE: To quantify how Satb2 mutations affect cell proliferation, survival, and differentiation using mouse bone cells (osteoblasts) modified with the CRISPR/Cas9 system to harbor different mutations in the Satb2 gene.

Images of Satb2-mutant pre-osteoblasts showing potential disease phenotypes. Left: Two cells that have divided retain a chromatin bridge (DNA shown in blue). Middle: A large cell with an abnormal, “donut-like” nucleus and nuclear blebs. Right: DNA is shown in pink, tubulin is shown in green. This mutant cell has an abnormally shaped nucleus with nuclear blebbing.

  • DIFFERENCES IN NEURONAL AND BONE DIFFERENTIATION IN SAS: To investigate differences in neuronal and bone differentiation using human induced pluripotent stem cells (HiPSCs) derived from individuals with SAS with different molecular alterations. We will be able to further test the effect of different mutation types on cellular defects. A major goal of this work is to identify penetrant phenotypes that can be used to assess the impact of pharmacological compounds as potential treatments for disease.

Human fibroblasts derived from skin biopsy from an individual with SAS. Nuclei are stained with Dapi (blue). The fibroblast marker (HSP47, also known as SERPINH1) is shown in red.