The Gabriella Miller Kids First Pediatric Research Program is pleased to announce a series of new releases for its publicly available data in pediatric cancer. These recent releases were added to the program’s Data Resource Center collaborative pediatric research effort and are accompanied by a series of data and program updates. The program’s pediatric cancer data releases include:

• On September 26, 2022, Gabriella Miller Kids First Pediatric Research Program released data on Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL). The primary goal in the treatment of T-ALL is to prevent relapse, which requires accurate risk stratification. No genetic alterations have been identified to date that reproducibly predict relapse independent of residual disease. Research led by Dr. David T. Teachey of the Children’s Hospital of Philadelphia involved the selection of approximately 1,350 cases of T-ALL from children and young adults treated through a clinical trial. These cases were submitted for sequencing of tumor DNA and RNA and original patient DNA. This included: whole genome sequencing, whole exome sequencing, and transcriptome profiling of tumor DNA/RNA and whole genome sequencing of germline DNA. Read more about the clinical trial.

Updates to Existing Data Releases:

• Effective October 6, 2022, the NICHD GMKF Enchondromatoses Study has been updated to version 2 in the dbGaP system. The public study report page may be browsed at dbGaP.
• Effective October 21, 2022, the NCI GMKF Kidney UT Malformations Study has been updated to version 2 in the dbGaP system. The public study report page and summary-level phenotype data may be browsed at dbGaP.

The Kids First program looks forward to a number of additional releases in the near future.  To learn more about Kids First previously Funded Research, visit the program website.

The Gabriella Miller Kids First Pediatric Research Program is pleased to announce a series of new releases for its publicly available data in structural birth defects. These recent releases were added to the program’s Data Resource Center collaborative pediatric research effort and are accompanied by a series of data and program updates. The program’s structural birth defects data releases include:

• On September 7, 2022, Kids First released data from a funded study on Cornelia de Lange Syndrome (CdLS), which is described by development delays, cognitive impairment, short stature, hearing loss, specific facial features, and structural birth defects such as differences of the limbs, heart, kidneys, and GI tract. Led by Dr. Ian Krantz of the Children’s Hospital of Philadelphia, this work is poised to lead to the identification of genetic causes and candidate genes for isolated birth defects seen together in similar diagnoses.
• On August 25, 2022, Kids First released data from the Kids First Bladder Exstrophy, Epispadias, Complex (BEEC) ​study. Patients with BEEC suffer significant illness and mortality due to impaired genito-urinary dysfunction. Led by Dr. Angie Jelin of Johns Hopkins University, this work shows how critical discovering this condition’s underlying genetic components is to understanding  its developmental signaling pathways and is likely the first step to developing targeted therapy.

Updates to Existing Data Releases:

• Effective October 6, 2022, the NICHD GMKF Enchondromatoses Study has been updated to version 2 in the dbGaP system. The public study report page may be browsed at dbGaP.
• Effective October 21, 2022, the NCI GMKF Kidney UT Malformations Study has been updated to version 2 in the dbGaP system. The public study report page and summary-level phenotype data may be browsed at dbGaP.

The Kids First program looks forward to a number of additional releases in the near future.  To learn more about Kids First previously Funded Research, visit the program website.

Whole genome sequence data for the “Genetic Contribution to Ewing Sarcoma in 330 parent-Offspring Trios” project (Accession Number: phs001228) are now available to the biomedical research community. 

Ewing sarcoma (ES) is a pediatric bone cancer that occurs in children and adolescents. This project, led by Dr. Joshua Schiffman, was selected for sequencing in 2015 will help us understand the genetic basis of ES. Furthermore, this cohort was selected for additional sequencing in 2017, and those data will be made available in the future. 

To search, access, and analyze this dataset, apply for access through NIH’s Database of Genotypes and Phenotypes (dbGaP): https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001228.v1.p1. Once approved, a user will receive instructions from dbGaP on how to access the data housed by the Kids First Data Resource Center (DRC). For help, you may contact support@kidsfirstdrc.org. 

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Orofacial clefts (OFCs) are structural birth defects which occur when a baby’s lip or mouth does not form properly during pregnancy and are some of the most common birth defects. Children with OFCs often have hearing loss, dental problems, and difficulties with eating and speaking. Identifying genetic factors contributing to OFCs could help improve diagnostics, treatments, and outcomes of OFCs.

Children with OFCs also have an increased risk of developing certain types of cancers (like breast, brain, and colon cancers), suggesting a shared genetic pathway between these disorders. The NIH Common Fund’s Gabriella Miller Kids First Pediatric Research (Kids First) Program is helping scientists improve our understanding of the connection between structural birth defects and childhood  cancer by developing a large-scale database of genetic and clinical data from patients and their families with these conditions.                       
Scientists participating in the Kids First Program used genetic data accessible through the Gabriella Miller Kids First Data Resource Portal, to pinpoint a new gene region linked to the risk of OFCs on chromosome 21, near genes involved in facial development. This genetic study of OFCs is the first to involve large enough numbers of patients and their relatives to allow meaningful results.   

The researchers analyzed genetic data from 580 OFCs patients and their families of European and Colombian descent. The newly identified region on chromosome 21 is part of a larger region that had been previously reported in studies of people of European descent, but not those of Latin American descent, suggesting that genetic differences within a population could influence the risk of development of OFCs.

Identifying risk genes is often the first step to understanding a disease and allows for the development of novel therapeutic approaches. Further studies are needed to determine the biological impact of this newly identified gene region. Findings like these could help guide scientists to other genes that play a role in the relationship between structural birth defects and childhood cancer, as well as lead to the discovery of shared genetic pathways between these disorders. 

Reference

Mukhopadhyay, N., Bishop, M., Mortillo, M. et al. Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21. Hum Genet 139, 215–226 (2020). https://doi.org/10.1007/s00439-019-02099-1.

Whole genome sequence (WGS) and clinical data for the orofacial cleft (OFC) birth defects in Latin American families study (Accession: phs001420) are now available to the biomedical research community through the NIH’s Database of Genotypes and Phenotypes (dbGaP) and the Kids First Data Resource Portal. 

OFCs are among the most common birth defects that occur when a baby’s lip, palate, or both do not form properly during pregnancy. The goal of this project led by Dr. Mary L. Marazita of the University of Pittsburgh Center for Craniofacial and Dental Genetics, is to identify genetic variants causing OFC.  

To access and analyze this dataset apply for access through NIH’s dbGaP at https://www.ncbi.nlm.nih.gov/gap. Once approved, a user will receive instructions from dbGaP on how to access the data housed by the Gabriella Miller Kids First Data Resource Center. For help with this dataset, you may contact support@kidsfirstdrc.org.
 

Whole genome sequence (WGS) and phenotype data for the Disorders of Sex Development (DSD) study (Accession: phs001178) are now available to the biomedical research community through the NIH’s Database of Genotypes and Phenotypes (dbGaP) and the Kids First Data Resource Portal. 

DSD are congenital conditions that involves abnormalities of sexual development. The goal of this project led by Dr. Eric Vilain, is to identify disease causing variants for DSD. 

To access and analyze these datasets apply for access through dbGaP. Once approved, a user will receive instructions from dbGaP on how to access the data housed by the DRC. For help with these datasets, you may contact support@kidsfirstdrc.org.
 

Whole genome sequence (WGS) data for the “Adolescent Idiopathic Scoliosis (AIS)” project (Accession:phs001410.v1.p1) are now available to the biomedical research community. 

AIS is a developmental defect of the spine and is the most common pediatric musculoskeletal defect. The goal of the project led by Drs. Jonathan Rios and Carol Wise, is to perform WGS to identify genetic causes of AIS. 

To search, access, and analyze this dataset, apply for access through NIH’s Database of Genotypes and Phenotypes (dbGaP) at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001410.v1.p1. 

Once approved, a user will receive instructions from dbGaP on how to access the data housed by the Kids First Data Resource Center (DRC). For help with this dataset, you may contact support@kidsfirstdrc.org. 

The Gabriella Miller Kids First Data Resource Center (DRC) has launched the Gabriella Miller Kids First Data Resource Portal, a centralized database of well-curated clinical and genetic sequence data from patients with childhood cancer or structural birth defects and their families. The portal includes sequence data from approximately 8,000 DNA and RNA samples and is expected to grow to 30,000 samples over the next few years. The Kids First Data Resource Portal will allow researchers everywhere access to vast amounts of pediatric genomic and clinical data to accelerate their research. Read more about the portal.

Kids First is pleased to announce the selection of a third set of childhood cancer and structural birth defects patient cohorts for whole genome sequencing. These patient cohorts will contribute to the forthcoming Kids First Data Resource which will allow scientists to identify genetic pathways that underlie these conditions and to explore whether shared genetic pathways exist between childhood cancer and structural birth defects. The applications were reviewed by a panel of external scientific experts and the selected cohorts address the following conditions:

• Developmental disorders of the skull (nonsyndromic craniosynostosis)
• Cleft lip and cleft palate (Orofacial Cleft Birth Defects)
• Developmental disorders of the chest muscle used for breathing (Congenital Diaphragmatic Hernia)
• Abnormal smallness of the face (Craniofacial Microsomia)
• Cancer in the bone or soft tissue (Ewing sarcoma)
• Noncancerous (benign) tumors developed in the blood vessels (infantile hemangiomas)
• Noncancerous tumors of cartilage that develop within the bones (Enchondromatoses)
• Patients with diagnoses of both childhood cancer and birth defects

The Kids First program will to call for applications to support whole genome sequencing of additional childhood cancer and structural birth defect cohorts in fiscal year 2018, pending availability of funds.

Whole genome sequence (WGS) data for the “Congenital Cranial Dysinnervation Disorders and Related Birth Defects” project (Accession Number: phs001247.v1.p1) are now available to the biomedical research community. 

Congenital Cranial Dysinnervation Disorders (CCDDs) are developmental abnormalities of one or more cranial nerves, typically resulting in weakness of eye and/or face movement. The goal of this project, led by Dr. Elizabeth Engle, is to generate WGS data to identify shared genetic pathways among CCDDs. This project will provide insight into the genetic aspects of CCDDs. 

To search, access, and analyze this dataset, apply for access through NIH’s Database of Genotypes and Phenotypes (dbGaP): https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001247.v1.p1.  Once approved, a user will receive instructions from dbGaP on how to access the data housed by the Kids First Data Resource Center (DRC). For help with this dataset, you may contact support@kidsfirstdrc.org. 
 

You can view abstracts for additional Kids First projects and estimated data release dates on the Kids First X01 project page. For questions regarding the Kids First program, please email: KidsFirst@od.nih.gov. 

In FY2015, Kids First selected the Genomic Analysis of Congenital Diaphragmatic Hernia cohort for whole genome sequencing. DNA sequence and clinical phenotype data for this project is now available in dbGap, and will be accessible through the forthcoming Kids First Data Resource. Until the Kids First Data Resource is completed researchers can visit the research projects page for the data release dates for each of the cohorts and the FAQs page for guidance on how to access the data.