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Aplastic Anemia, Boricua Mutation, Oligodendroglioma, cWGS Infants

Published on October 1, 2021 in Cornerstone Blog · Last updated 3 months 2 weeks ago


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In the News

limjr [at] (By Jillian Rose Lim)

This week's roundup of research headlines highlights the different ways Children's Hospital of Philadelphia scientists seek to deepen our understanding of conditions and challenges affecting children. Learn about a new method to diagnose a life-threatening bone marrow disorder, an exciting partnership to study a rare cancer in more complex detail, and how one scientist is spreading awareness of a gene mutation predominantly found in children of Puerto Rican descent. Furthermore, we report on new findings to support clinical whole genome sequencing in critically-ill newborns and the effect of gun violence exposure on mental health ED visits.

Researchers Develop Novel Method to Diagnose Aplastic Anemia

Currently, no diagnostic tests exist to differentiate aplastic anemia (AA), a life-threatening bone marrow disorder, from disorders that share similar symptoms, including inherited bone marrow failure syndromes (IBMFS). In a new study published in Blood Advances, CHOP researchers report that two laboratory findings can distinguish the autoimmune pathogenesis of AA from other disorders – thus supporting the speedier diagnosis and treatment of AA.

The researchers analyzed lab samples from 454 patients with AA, IBMF, and other hematologic diseases. They found that the two lab findings – acquired paroxysmal nocturnal hemoglobinuria (PNH) and copy-number neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) clones encompassing HLA genes had 100 percent positive predictive value for AA and could facilitate diagnosis in approximately half of AA patients.

"Our analysis demonstrates that PNH and 6p CN-LOH clones effectively distinguish AA from IBMFS, and both measures should be incorporated early in the diagnostic evaluation of suspected AA," said Daria V. Babushok, MD, PhD, senior study author and physician-scientist in the Comprehensive Bone Marrow Failure Center, in a press release. "The next frontier in BMF diagnostics will include combining these two assays with more sophisticated T-cell analyses and faster, more comprehensive somatic and germline genetic studies to improve the accuracy and efficiency of diagnosis of acquired and inherited BMF disorders."

Learn more.

CBTN Discusses Novel Approaches to Understanding Oligodendroglioma biology

The Children's Brain Tumor Network (CBTN) described a unique collaborative model to facilitate deeper understanding of oligodendroglioma, one of the rarest forms of brain and central nervous system (CNS) cancer in children and adults. In a news item published on the CBTN's website, Jonathan Waller, senior communications associate in our Center for Data-Driven Discovery and Biomedicine (D3b), described the expanded partnership of Project Open Oligo, which now includes participation from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) alongside CHOP, the University of Pennsylvania, the Barrow Neurological Institute, Oligo Nation, and CBTN.

As pioneers in the characterization of tumors through proteogenomic analysis, CPTAC will perform full proteomic data generation and proteogenomic data integration of every tumor sample provided by CBTN, ON, and CHOP – thus yielding a more complete understanding of cancer biology. Historically, oligodendroglioma has been challenging to study due to its rarity and lack of access to high-quality oligo biospecimens and molecular data.

"When complete, this partnership will produce the largest and most molecularly annotated collection of oligodendroglioma data ever generated and shared with the public as a community resource," Waller wrote. "The implications for scientific discovery are tremendous."

Adam Resnick, PhD, director of D3b, also commented: "Not only is this collaboration an exciting new venture into biomedical research, but also a significant triumph for both the cancer and rare disease communities. Through this partnership between private foundations, research institutions, and government, a new course for innovative collaboration has been charted, and serves as a model for future discovery into rare illnesses in children and adults."

Read more in the CBTN newsroom.

CHOP Neurologist Discusses Boricua Mutation on Univision

Our own Xilma Ortiz-Gonzalez, MD, PhD, a CHOP neurologist, was recently interviewed on Univision's "Despierta America" to discuss a gene mutation predominantly found in children of Puerto Rican descent. Dr. Ortiz-Gonzalez appeared on the segment, which is catered toward Spanish-speaking audiences, in order to reach those in Puerto Rico who may have children affected by the Boricua mutation. For several years, Dr. Ortiz-Gonzalez has studied the mutation found in the gene TBCK, as it can cause a variety of severe symptoms, including intellectual disability, epilepsy, progressive dysfunction in the central and peripheral nervous systems, and more.

Watch the interview.

Multi-institute Study Shows Effect of Whole Genome Sequencing on Precision Care for Critically-ill Infants

CHOP researchers published new findings from the NICUSeq Randomized Time-Delayed Trial in partnership with four collaborating children's hospitals and Illumina Inc., a developer of tools for DNA, RNA, and protein analysis. In JAMA Pediatrics, the researchers reported that clinical whole-genome sequencing (cWGS) outperformed usual care by two-fold when it came to diagnostic efficacy, as well as clinical management of acutely ill newborns suspected of having a genetic condition. The results highlight the importance of large-scale genetic testing in newborns that can help inform early diagnosis and precision care for pediatric patients.

"The clear and important link between establishing a diagnosis and improved care management lends much weight to the adoption of cWGS as a first-tier diagnostic test in critically-ill newborns," said Ian Krantz, MD, professor of Pediatrics at the Children's Hospital of Philadelphia, in a press release.

Notably, the 354 infants who made up the study population reflected the racial and ethnic diversity of US demographics, mirroring the real-world variability of infant care. Each infant had been admitted to an intensive care unit with a suspected genetic disease and were subsequently randomized to receive clinical WGS results early (15 days) or delayed (60 days). After a period of observation and analysis, the researchers found that in both groups, access to cWGS doubled the proportion of patients receiving a precision diagnosis for their condition and a change of clinical management.

Read the study abstract.

Exposure to Gun Violence Associated With Higher Rates of Mental health-related ED Visits

In a recent JAMA Pediatrics study, researchers from CHOP and the University of Pennsylvania report an association between exposure to neighborhood gun violence and increased odds of emergency department (ED) visits related to mental health. The study utilized data from CHOP's ED as well as the Philadelphia Police Department's repository of shootings (available on the city's open data website).

The researchers began by examining the number of ED visits from children ages 0 to 19 for mental health concerns (such as posttraumatic stress disorder, depression, intentional ingestion of harmful substances, and other psychiatric emergencies). They then cross-referenced that data to see how many of those children had been exposed to gun violence 60 days prior to their ED visit, with exposure to gun violence defined as whether they lived within four to five blocks of a reported shooting.

The team found that of the 2,629 reported shootings in the data set, 31 percent had one or more corresponding mental health-related ED visits in the 60 days after the shooting. Those children residing within two or three blocks of a shooting incident had greater odds of having a mental health-related ED visit.

"Gun violence affects the whole community, beyond the victims who are personally injured," said lead author Aditi Vasan, MD, MSHP, hospitalist and health services researcher at CHOP. "Now that we have confirmed exposure to shootings negatively impacts the mental health of children, we can work to develop ways to provide preventive and responsive support for children and families exposed to neighborhood gun violence."


Catch up on our headlines from our Sept. 17 In the News:

  • CHOP Awarded Gold Resuscitation Quality Achievement Award
  • Human Developmental Cell Atlas: Opportunity to Study Human Development at Cellular Level
  • Pilot Study Shows Novel Device Helps HI Patients With Diabetes Maintain Stable Glucose Levels
  • CHOP Researchers Study Executive Functioning Challenges for Autistic Children in School

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