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Publications

Date Revised: December 2025

Thank you to all the families for participating in Simons Searchlight. Through your involvement, we aim to assist researchers and geneticists worldwide in understanding genetic disorders affecting you or your family.

The research conducted using Simons Searchlight data has resulted in numerous published papers. These papers undergo a peer-review process, where other scientists assess and validate the research before publication in scientific journals. Additionally, some findings are shared via preprints, allowing rapid dissemination of information to the scientific community.

Many of the publications feature the name “Simons Variation in Individuals Project” (SimonsVIP), which was the original name of our research program, now known as Simons Searchlight.

The listed articles are organized from newest to oldest. You can explore publications by specific genetic conditions using the categories below.

As of December 2025, Simons Searchlight has contributed to 135 publications and preprints, and we will continue to summarize new publications.

For accessibility, the Simons Foundation encourages researchers to make their publications open access. If you cannot access a journal article, we recommend reaching out to the last author listed on the paper to request a copy.

Understanding Publication Reference Titles:

-The article title is followed by publication details, including where and when it was published.
– If there are more than three authors, we use “et al.” to represent additional contributors.
– Journals are referenced using shorthand names.

Disclaimer: Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication. In contrast, all other articles listed here have undergone review by fellow researchers to ensure quality and accuracy. While posting on medRxiv or bioRxiv allows researchers to share findings quickly, the final published results may differ after undergoing formal peer review for journal publication.

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Genetic Condition
Year of Publication
134 Publications
Copy number variants and the tangential expansion of the cerebral cortex
  • This study used brain imaging from several different genetic cohort studies to see if there was a relationship between cortical surface area and copy number variant genetic variation. The researchers also wanted to see if region-specific, cell-specific, and time-specific gene expression played roles in shaping the development of cortical surface area. Show More
  • Cortical surface area refers to the outer area of the brain region, which is called the cortex (also known as the cerebral cortex). This is the outermost layer of the left and right sides of the brain. During the process of brain development starting in utero, the brain develops folds and this results in more surface area of the brain structure. Abnormal development of the cortical surface area is linked to neurodevelopmental conditions.
  • The cortical surface area is part of the brain that is important for thinking, voluntary movements, language, reasoning, and perception.
  • The researchers used Simons VIP (Simons Searchlight from 2010-2014) MRI brain imaging data from people with 16p11.2 deletions and duplications, people with 1q21.1 deletions and duplications, and family members without deletions or duplications. The study also included MRI brain imaging data from other research groups.
  • The researchers found that people with 16p11.2 or 1q21.1 deletions or duplications had a smaller cortical surface area compared with people without these copy number variants. People with 16p11.2 or 1q21.1 deletions had a smaller cortical surface area compared with people with these duplications. Show Less
Nat Commun 16, 1697 (2025)
Liao et al.
Full Article

16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
2025

Differential links in 16p11.2 deletion carriers reveal aberrant connections between large-scale networks
  • The researchers used imaging and survey data from 26 Simons Searchlight participants with a 16p11.2 deletion and 41 age-matched people without a genetic diagnosis to investigate the brain connectivity differences in each group. Show More
  • The researchers studied the different brain patterns that light up on the MRI, which is called functional connectivity.
  • People with a 16p11.2 deletion had different functional connectivity of the brain than people with no genetic diagnosis. One hot spot of activity in people with a 16p11.2 deletion was linked to the region of the brain needed for processing speech sounds, which is similar to findings in other research studies.
  • The researchers also found other patterns, such as the way the brain lights up differently for people with lower communication and social adaptive behaviors. Show Less
Cereb Cortex 35, bhae474 (2025)
Qureshi et al.
Full Article

16p11.2 deletion
2025

Direct pathway bias and altered striatal neurogenesis in human iPSC models of 16p11.2 CNVs: Evidence from single-cell and functional analyses
  • The researchers investigated how a specific brain pathway called a striatal circuit is changed in people with a 16p11.2 deletion or duplication. A striatal circuit controls motor movement and is influenced by thoughts, emotions, and personal motivations. Show More
  • The researchers used 3 16p11.2 deletion and 3 16p11.2 duplication induced pluripotent stem cells (iPSCs) from Simons Searchlight participants. The researchers turned the iPSCs into striatal brain cells in the lab.
  • The researchers found that striatal 16p11.2 deletion cells divided more often and took longer to divide than cells with no genetic condition, and that striatal 16p11.2 duplication cells divided less often and faster than cells with no genetic condition. The researchers suggested that these reciprocal features of the cells are consistent with what has been reported in humans with deletion carriers having a larger than average head size and duplication carriers having a smaller than average head size.
  • Even though the cells behaved differently when growing and dividing, the researchers found that these copy number variant striatal cells favored one subtype in both deletion and duplication carriers. This could explain why having a deletion or duplication can be linked to similar neurodevelopmental conditions, such as autism, intellectual disability, and ADHD. Show Less
bioRxiv Preprint, (2025)
Fjodorova et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025

Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility
  • Many people with neurodevelopmental conditions experience gastrointestinal (GI) issues, such as constipation and diarrhea. Show More
  • The researchers in this study used a combination of Simons Searchlight genetic and clinical data, human tissue samples, and a frog model to study how genetic variants associated with autism affect the GI system.
  • The researchers looked at the percent of people who had GI symptoms and one of the following conditions: SYNGAP1, CHD8, ADNP, SCN2A, FOXP1, CHD2, GRIN2B, ARID1B, SLC6A1, DYRK1A, STXBP1, MED13L, CTNNB1, ANKRD11, CSNK2A1, and PACS1. GI issues were reported for all of these conditions, and the average frequency of GI issues was about 52 percent.
  • The genetic conditions and GI issues identified were similar to those identified using Citizen Health medical record data for the 5 genes with available Citizen data: SYNGAP1, CHD8, SCN2A, CHD2, and DYRK1A. Within these 5 genetic conditions, gut dysmotility, and specifically constipation, were the most common GI issues. GI motility is controlled by neurons in the GI tract (known as the enteric nervous system). The researchers think that genetic variants in these genes might affect the development or function of the enteric nervous system.
  • The researchers then used frog models for SYNGAP1, CHD8, SCN2A, CHD2, and DYRK1A. Genetic variants in these genes affected the early development of the enteric nervous system. This suggests that even though these genes work in different cellular pathways, they can affect this early developmental process.
  • Finally, the researchers found that a depletion of DYRK1A resulted in gut dysmotility. The researchers treated the frogs with drugs that affect serotonin. Serotonin is a chemical that works as a signal between brain cells. It also controls the enteric nervous system and gut motility. The researchers were able to return gut motility to normal in the frog model.
  • This research furthers our understanding of the link between GI symptoms and autism-associated genes. Show Less
Nat Commun 16, 2238 (2025)
McCluskey et al.
Full Article

ADNP
ANKRD11
ARID1B
CHD2
CHD8
CSNK2A1
CTNNB1
DYRK1A
FOXP1
GRIN2B
MED13L
PACS1
SCN2A
SLC6A1
STXBP1
SYNGAP1
2025

Clinical and neuropsychological phenotyping of individuals with somatic variants in neurodevelopmental disorders
  • The researchers studied Simons Searchlight participants who were mosaic for neurodevelopmental genetic variants. Show More
  • Being mosaic for a genetic variant means that a person has some cells with the genetic variant and other cells that do not have the genetic variant. People who are mosaic for a genetic variant have a genetic change that happened after conception, but usually during the earlier stages of pregnancy. These changes happen spontaneously and are not a result of something that happened or was taken during pregnancy.
  • For people who are mosaic for a genetic variant, the number of cells with the genetic variant is different in different parts of the body. For example, when doing genetic testing on a person's blood sample, the amount of cells with the genetic variant might be different than if using another tissue type for genetic testing.
  • The researchers use the term ‘somatic’ to indicate someone who is mosaic for a neurodevelopmental gene, and ‘germline’ to indicate someone who is born with only the genetic variant detected.
  • 15 people with pathogenic or likely pathogenic mosaic variants across 10 genetic disorders were identified in Simons Searchlight. The genes affected were CHD8, HIVEP2, SCN2A, STXBP1, SYNGAP1, CTNNB1, IRF2BPL, NEXMIF, PPP2R1A, and distal 16p11.2 deletion. Eight people had detailed clinical information available.
  • People who were mosaic for pathogenic or likely pathogenic variants showed a spectrum of medical conditions and traits. All people had diagnoses of developmental delay and/or language delay, about one-half had hypotonia and/or autism diagnoses, and smaller subsets of people had diagnoses of epilepsy, cortical visual impairment (CVI), large head size (macrocephaly), and small head size (microcephaly).
  • People who were mosaic for pathogenic or likely pathogenic variants showed a range of adaptive functioning, social and communication skills, social and related behaviors, and emotional and behavioral symptoms.
  • The researchers did a comparison of medical features between people who were mosaic and those with germline variants (people with cells that had only the genetic variant). The results suggested that people who are mosaic for a neurodevelopmental genetic variant had either similar or less severe clinical features than those with germline variants in the same gene. Show Less
Neurol Genet 11, e200254 (2025)
Mo and Walsh
Full Article

16p11.2 distal deletion
CHD8
CTNNB1
HIVEP2
IRF2BPL
NEXMIF
PPP2R1A
SCN2A
STXBP1
SYNGAP1
2025

Pathogenic PPP2R5D variants disrupt neuronal development and neurite outgrowth in patient-derived neurons that are reversed by allele-specific knockdown
  • The researchers used induced pluripotent stem cells (iPSCs) derived from Simons Searchlight participants with PPP2R5D variants to understand how these variants affect neuronal development and to test a potential new treatment approach. iPSCs are a special type of cells that can be turned into other body cells, making it easier to study parts of the body that are difficult to get samples of, such as brain cells. Show More
  • The researchers studied iPSCs from people with p.Glu198Lys and p.Glu420Lys variants because they suspected that people with these variants have a more severe neurodevelopmental condition than people with other PPP2R5D variants. The researchers were interested in how cells with these variants compared with a cell line with a complete deletion of the PPP2R5D gene.
  • Brain iPSCs with the p.Glu198Lys and p.Glu420Lys PPP2R5D variants grew more than iPSCs without the variants. Brain cells and neurons made from iPSCs with the variants showed increased growth of connections than brain cells and neurons made from iPSCs without the variants.
  • These variants altered genetic pathways that are involved in brain cell growth, function, and processes needed for cells to connect to each other.
  • These results were not found in the cells that had the PPP2R5D gene deletion. This suggests that the genetic condition associated with PPP2R5D-related syndrome is a result of altered function of the PPP2R5D protein, not a loss of the PPP2R5D protein.
  • Antisense oligonucleotides (ASOs) can be used to target specific pieces of RNA that make proteins. The researchers made ASOs to target only the RNA with the problematic p.Glu198Lys variant. They studied how much RNA was produced (also known as gene expression) from the targeted variant before and after ASO treatment.
  • They found that ASO treatment for p.Glu198Lys reversed the brain cell overgrowth.
  • This research provides a better understanding of the molecular and cellular effects of PPP2R5D variants, as well as insight into potential therapies. Show Less
HGG Adv 6, 100450 (2025)
Young et al.
Full Article

PPP2R5D
2025

Accessibility and utilization of genetic laboratory reports: A comprehensive analysis of factors impacting access and use across borders
  • In this Master’s thesis, the author used data from a survey created by Kaitlyn Singer, research project manager for Simons Searchlight, that was conducted between April 2022 and January 2023. Singer developed a 15-question survey designed to assess participants’ level of knowledge about their genetic condition, care received from different providers, resources received, and laboratory testing. Show More
  • The survey was sent by email blast to Simons Searchlight participants, and a total of 622 surveys were completed.
  • The author found that genetic-result disclosure appointments taking 30 minutes or less with a genetics provider correlated with a higher frequency of participants leaving with their questions unanswered. Appointment times between 30 minutes and 1 hour resulted in a higher level of appointment satisfaction.
  • Genetic result disclosures from a geneticist or genetic counselor resulted in higher levels of satisfaction. In addition, participants who received their results from a genetic counselor were more likely to report that their questions had been answered during the appointment. In contrast, those who received results from a neurologist or primary care provider were more likely to report that their questions had not been answered.
  • While most people did report receiving their genetic testing report at the time of results disclosure, about 20 percent did not receive a report at the time of disclosure.
  • Some of the data from international participants (outside the U.S.), suggested that receiving a result from a geneticist was associated with a higher proportion of participants reporting that their questions were not answered, with no differences identified between receiving a result from a genetic counselor, neurologist, or “Other” provider.
  • This research suggests that shorter appointment times with less specialized professionals might lead to more unresolved questions from families. Show Less
University of Pittsburgh ProQuest Dissertations & Theses, 31995165 (2025)
Lopez-Jimenez
Full Article

All Genes
2025