Publications

Date Revised: January 2024

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 chronologically, from oldest to newest. You can explore publications by specific genetic conditions using the categories below.

As of April 2024, Simons Searchlight has contributed to 98 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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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
98 Publications
Identifying cell type specific driver genes in autism-associated copy number loci from cerebral organoids
  • The goal of this research was to study what genes are turned on and off in the different cell types of the brain in people with a copy number variant (CNV). A CNV happens when there is a change in a section of DNA that results in a gene or several genes being deleted or duplicated. 16p11.2 deletion is an example of a CNV.Show More
  • The researchers used induced pluripotent stem cells (iPSCs) of a) nine 16p11.2 deletion Simons Searchlight participants, b) four participants with a 15q11-13 duplication, and c) twelve participants with no genetic changes from a different biobank. The iPSCs were used to create mini-brains in the laboratory. Researchers are able to make mini-brains that communicate with each other, similar to how a brain does in a human, but mini-brains are less complex than human brains.
  • Studying CNVs is difficult because people with a CNV have several genes deleted or duplicated. This makes it hard to know what genes could be affecting different parts of human development.
  • The researchers developed a new process to sequence and analyze individual cells from the mini-brains. They used a technique called CRISPR/Cas9 to edit the brains and confirm their genetic findings.
  • The researchers found three genes within the 16p11.2 region that might affect brain cell development. They genes were YPEL3, KCTD13, and INO80E.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Nat Commun 13, 3243 (2022)
Lim et al.
Full Article

Tags:

16p11.2 deletion
16p11.2 duplication
2022
Neurodevelopmental profile of HIVEP2-related disorder
  • This is the first publication on HIVEP2 that includes Simons Searchlight data.Show More
  • This study included 12 children aged 3 to 13 years old with a pathogenic or likely pathogenic HIVEP2 genetic variant. This study adds to what is known about HIVEP2, as only 14 people have been described in medical research.
  • The researchers found that 3 out of 12 children had seizures, half of the children had autism, and everyone had an intellectual disability. Many children had language impairment and gastroesophageal reflux, and most had low muscle tone. The details of all the medical features found in this group of children are organized in a table in the paper.
  • The researchers suggested that an increase in autism symptoms was associated with lower adaptive functioning in people with a HIVEP2 genetic variant. Adaptive functioning refers to how a person handles common demands in day-to-day life. The researchers also suggested that autism was underdiagnosed in people with a HIVEP2 genetic variant.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Dev Med Child Neurol 64, 654-661 (2022)
Mo et al.
Full Article

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HIVEP2
2022
Diagnostic preferences include discussion of etiology for adults with cerebral palsy and their caregivers
  • Children and adults who get a diagnosis of cerebral palsy are diagnosed with a motor issue. Cerebral palsy is a non-progressive movement disorder, and the diagnosis does not tell you the source of the issue. Many genetic conditions can cause cerebral palsy issues.Show More
  • The researchers explained that there is some controversy among doctors about providing a cerebral palsy diagnosis when the condition is associated with a genetic origin. This is unlike when people are diagnosed with autism or epilepsy, which are also diagnosed medically and can be genetic in origin.
  • The researchers surveyed people who were diagnosed with cerebral palsy, and their caregivers, to understand their feelings about this neurodevelopmental condition.
  • The researchers sent their survey to people who were part of the Cerebral Palsy Research Network and Simons Searchlight. This included 16 groups in Simons Searchlight: 16p11.2 deletion, 1q21.1 deletion, ADNP, ASXL3, CHAMP1, CSNK2A1, CTNNB1, DYRK1A, GRIN2B, HIVEP2, PPP2R1A, PPP2R5D, PCHD1, SCN2A, STXBP1, and SYNGAP1.
  • There were 197 participants, and the survey was sent between December 2019 to May 2020.
  • Importantly, most participants did not have a genetic diagnosis associated with their cerebral palsy, and the most common cause of cerebral palsy in this group was a brain injury. Only half of the people in this study have been told the origin of their cerebral palsy.
  • Three out of four participants said that they valued knowing the cause of their cerebral palsy. Many participants valued having a cerebral palsy diagnosis over only having a genetic diagnosis because it allowed them to anticipate how their symptoms would progress, to explain their symptoms to others, to gain access to services, and to understand the cause of their symptoms.
  • The researchers found that people with cerebral palsy, and their caregivers, overall preferred having a genetic diagnosis and a cerebral palsy diagnosis.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Dev Med Child Neurol 64, 723-733 (2022)
Aravamuthan et al.
Full Article

Tags:

16p11.2 deletion
1q21.1 deletion
ADNP
ASXL3
CHAMP1
CSNK2A1
CTNNB1
DYRK1A
GRIN2B
HIVEP2
PCHD1
PPP2R1A
PPP2R5D
SCN2A
STXBP1
SYNGAP1
2022
Contrastive machine learning reveals the structure of neuroanatomical variation within autism
  • These researchers used brain imaging and computer software to identify the brain structure patterns in people who have autism. They used the Autism Brain Imaging Data Exchange I (ABIDE I) magnetic resonance imaging (MRI) dataset of 470 people with autism to create the main imaging theories. They compared the imaging of people with autism to 512 images of people without autism.Show More
  • Then the researchers used 121 images from Simons Searchlight 16p11.2 data to validate what they found and to see if they could identify people who have an autism diagnosis.
  • The researchers noticed variations in people's brain structures and that some parts of the brain are harder to image than others. They found that autism-specific brain structures are different at different ages, so comparisons should be made within age groups, not across ages. They also noted that because of the large variation in brains, it is hard to know which differences are due to normal brain variation and which differences are due to autism. So, the same brains should be studied over time to learn how they develop.
  • Their computer model was able to identify individual brain structure patterns specific to autism and relate them to a participant’s clinical features, such as repetitive behaviors and adaptive behavior. The researchers used Simons Searchlight data to re-confirm the findings from their ABIDE I data.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Science 376, 1070-1074 (2022)
Aglinskas et al.
Full Article

Tags:

16p11.2 deletion
16p11.2 duplication
2022
Consistency of parent-report SLC6A1 data in Simons Searchlight with provider-based publications
  • To study the strength of parent-reported data in Simons Searchlight, these researchers did a side-by-side comparison of the medical features of people with SLC6A1 genetic variants, as reported by parents and as reported in medical publications.Show More
  • It can be difficult to have patients of a global rare disease community to be studied by the same set of doctors, Simons Searchlight provides a unique opportunity for researchers to study the community online also allows more people to participate.
  • The researchers compared 116 people with SLC6A1 genetic variants that were described in medical publications to 43 people in Simons Searchlight.
  • When comparing the parent-reported data and the provider-reported information, there was the fewest number of missing data points for conditions, such as epilepsy and autism. The provider-reported data missed some clinical features that the parents found.
  • The researchers found no difference in the frequency of developmental delay, autism, and attention deficit hyperactivity disorder between either group. However, they found that parents reported a slightly higher frequency of low muscle tone and movement issues than people who were seen by a medical doctor. People who were seen by doctors were more likely to be described to have epilepsy, but the difference was not large.Show Less
J Neurodev Disord 14, 40 (2022)
Bain et al.
Full Article

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SLC6A1
2022
Characterization of phenotypic range in DYRK1A haploinsufficiency syndrome using standardized behavioral measures
  • This is the first publication on DYRK1A that includes Simons Searchlight data.Show More
  • This study included 24 children with a pathogenic or likely pathogenic DYRK1A genetic variant. This was the first paper to include 18 of the participants; the other six participants have been included in previous papers. The 18 participants add to what is known about DYRK1A, as only 79 people have been described in medical research.
  • DYRK1A stands for dual-specificity tyrosine phosphorylation-regulated kinase 1A, and it is important for brain cell development and survival in the very early stages of human development.
  • The paper includes tables that show the genetic and clinical information of the participants.
  • Genetic changes that cause DYRK1A-related syndrome are loss of function variants that lead to one copy of DYRK1A not being functional. Many participants had developmental issues that were seen prenatally by ultrasound. Almost all participants were smaller than average in both height and weight.
  • All participants had intellectual disability and a smaller than average head size. About half had seizures at some point. Most participants had delayed or absent speech and delayed walking. About half received a diagnosis of autism.
  • Constipation and gastroesophageal reflux disease were common for these participants.
  • Participants’ adaptive behavior scores were in the low range. Adaptive functioning refers to how a person handles common demands in day-to-day life.
  • The most common issues for preschool children were being withdrawn and having attention difficulty, whereas the most common issues for school-age children were social, thought, and attention issues.
  • The researchers compared what they found in the Simons Searchlight group to the information on the 79 people reported in other papers. They found the medical information to be similar, but they were able to get more detailed information from the Simons Searchlight data.Show Less
Am J Med Genet A 188, 1954-1963 (2022)
Fenster et al et al.
Full Article

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DYRK1A
2022
Clinical, neuroimaging and molecular characteristics of PPP2R5D-related neurodevelopmental disorders: An expanded series with functional characterisation and genotype–phenotype analysis
  • This is the first publication on PPP2R5D that focuses on Simons Searchlight data.Show More
  • PPP2R5D stands for protein phosphatase 2 regulatory subunit B delta. In cells, PPP2R5D is an enzyme that adds a molecule called a phosphate to the amino acids serine and threonine.
  • This study includes 72 Simons Searchlight participants with a pathogenic or likely pathogenic genetic variant in PPP2R5D. This adds to the 31 people with PPP2R5D genetic variants that have been published to date in the medical literature.
  • The researchers studied the function PPP2R5D genetic variants and grouped the variants into three different categories.
  • Participants ranged in age from 1 to 45 years old. Most participants had low muscle tone and a larger-than-average head size. About half of the participants had seizures, with an average age of seizure onset at just over 2. Seizure activity varied between participants: some had more than 100 seizures a day, others had one a year.
  • Participants had the most difficulty with expressive communication and personal daily living skills. About 1 in 3 participants had acid reflux and constipation.
  • The researchers found that about 1 in 5 participants had developmental delay or intellectual disability, which is lower than what other studies have reported.
  • The researchers looked at if there was any link between genetic variants and medical features. Most people with a Glu198Lys and Trp207Arg had the most consistent set of medical features, both of these variants are in the same functional category.
  • This was the largest study to date of participants with a PPP2R5D genetic variant. For the first time, researchers were able to investigate on a large scale the function that genetic variants have in the cell in relation to clinical features.Show Less
J Med Genet Epub ahead of print, (2022)
Oyama et al.
Full Article

Tags:

PPP2R5D
2022