Publications

Date Revised: October 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 October 2024, Simons Searchlight has contributed to 108 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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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
108 Publications
Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes
  • Studying social and cognitive ability in people with neurodevelopmental genetic syndromes is hard not only because the conditions are rare, but also because it requires the detection of subtle differences. Being able to see even small changes in social and cognitive ability in a person is important to assess the effectiveness of a drug or personalized medicine.Show More
  • In this study, the researchers created a webcam-based eye tracking method that uses the camera on the participants' home computer or laptop to detect where participants look when shown videos and images. This was the first time that researchers tried to develop a multi-condition wide method for use remotely without a clinician, and for use in people with intellectual disability.
  • The researchers recruited participants through patient advocacy organizations and Simons Searchlight, and they used participant information within the Simons Searchlight database. Participants were between the ages of 3 and 45 years old. Genetic communities that participated through Simons Searchlight included GRIN2B, CSNK2A1, HIVEP2, SCN2A, MED13L, and STXBP1.
  • The study included 375 participants, including 163 with a neurodevelopmental genetic syndrome, 56 with a neurodevelopmental condition but no genetic diagnosis, and 156 without any neurodevelopmental issues. The researchers used artificial intelligence to analyze the participant recordings, and they collected caregiver-reported surveys.
  • Participants were surveyed with this new measure at 3 different times. The survey looked at various parts of social attention, how much vocabulary was understood, how fast information was processed, and single-word reading.
  • The researchers found that in all areas evaluated, there was strong evidence of validity, suggesting that this method could be consistent and reliable for this community. One exception was within the social domain that measures positive and negative emotional expression.
  • Participants with intellectual disability had lower levels in all of the following measures: attention, intentionally reviewing the screen, social attention and preference, single-word reading, speed of recognizing images on screen, and understanding vocabulary.
  • In general, participants with a neurodevelopmental genetic syndrome showed a more impaired neurobehavioral condition, including lower attention, higher nonsocial preference, worse ability to understand vocabulary and single-word reading, and slower speed to faces and objects.
  • Some genetic conditions were found to have group patterns. For example, the participants with SYNGAP1 had higher scores for negative emotional expressiveness.
  • The researchers suggested that this new method could be used consistently for people with mild to moderate cognitive disability, but that consistency could be lower for people with severe cognitive disability.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Am J Med Genet C Semin Med Genet. 193, e32058 (2023)
Frazier et al.
Full Article

CSNK2A1
GRIN2B
HIVEP2
MED13L
SCN2A
STXBP1
2023

Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles
  • Many people with autism also have gastrointestinal issues, such as constipation, diarrhea, or abdominal bloating. To understand why this might be, researchers have focused on the gut-brain connection by studying the links between hormones, the immune system, and the nervous system.Show More
  • The gut microbiome is the set of bacteria, archaea, fungi, and viruses that live within a person’s intestine and help with digestion.
  • A disruption in the gut-brain connection (also called the gut-brain axis) has been suggested to play a role in neurodevelopmental disorders. Studies on the microbiome in autism have not had consistent findings.
  • In this study, the researchers compared 25 different studies and datasets to identify patterns in people with autism. These studies had 1,193 samples, including blood, urine, and fecal samples. The researchers used 16p11.2 deletion data from Simons Searchlight.
  • The researchers had difficulty in identifying a pattern between studies because the findings were more consistent within studies than between studies. They suggested that this might be due to age, sex, or global location of the participants in each study.
  • In age- and sex-matched analyses, the researchers found a difference between the microbiome of children with autism and children without autism. The researchers called this an autism microbiome signal.
  • There may be a link between the microbiome and diet. The researchers found that autistic people have a lower intake of food enriched for certain amino acids that are important for helping the body to make neurotransmitters. Neurotransmitters are biological messengers that carry chemical signals from one brain cell to the next.
  • The researchers found that a core microbiome made up of Bacteroides, Prevotella, Bifidobacteria, Desulfovibrio, and multiple butyrate producers is linked to autism. This finding suggests that that gut microbiome may play a role in shaping autism symptoms.
  • The researchers did not find any link between a specific genetic variation and a person’s microbiome.
  • The researchers concluded that our understanding of the link between the gut and the brain in autism is still very limited, and that more studies are needed for larger conclusions to be possible.Show Less
Nat Neurosci. 26, 1208-1217 (2023)
Morton et al.
Full Article

16p11.2 deletion
All Genes
2023

The immune status of patients with 16p11.2 deletion syndrome
  • Within the usual 16p11.2 deletion region, also known as the proximal deletion, there are several genes that are important for immune function. The immune genes within the 16p11.2 region are CORO1A, MAPK3, and SPN. There are a few other immune-associated genes just outside the region.Show More
  • The researchers wanted to know if there was an association between having a 16p11.2 deletion and immune issues.
  • In this study, the researchers used information provided by 170 Simons Searchlight participants with a 16p11.2 deletion.
  • Most participants, 138 out of 170 (81 percent) reported that they had a history of infections that were significant. The most common infection category was ear infections occurring more than 8 times, followed by respiratory infections and pneumonia. Eleven participants (6.5 percent) reported that they had a diagnosis of an immunodeficiency. These findings were similar to the findings in participants with a 16p11.2 deletion that were recruited by researchers at Children’s Hospital Colorado.
  • The researchers compared their findings to a group of participants who do not have a 16p11.2 deletion, and there were no reported concerns for a history of infection or autoimmune issues for that comparison group.
  • The article contains a detailed table of all reported infections for people with and without a 16p11.2 deletion.
  • The researchers suggested that people with a 16p11.2 deletion might benefit from extra immunological evaluation by their managing provider.Show Less
J Clin Immunol 43, 1792-1795 (2023)
Wang et al.
Full Article

16p11.2 deletion
2023

Receptive language and receptive-expressive discrepancy in minimally verbal autistic children and adolescents
  • Speaking communication is very difficult for about 30 percent of autistic people, and many will not be able to speak well into adulthood, also known as minimally verbal. The researchers aimed to learn how much people who are minimally verbal can understand when spoken to. This type of understanding is called receptive language.Show More
  • Using parent reported surveys and assessments, the researchers measured nonverbal cognitive abilities in the participants to understand their level of receptive language.
  • Children and adolescents between the ages of 5 and 18 with an autism diagnosis were included in this study. Participant data was used from Simons Searchlight, Simons Simplex Collection, and Autism Inpatient Collection, as well as the National Database for Autism Research. The study included 1,579 minimally verbal participants.
  • The researchers found that on average, children and adolescents who were minimally verbal had lower receptive language than age-matched peers. In addition, as children became older, the differences in receptive language were greater.
  • However, for the group, receptive language scores were higher than expressive language scores, suggesting that participants were able to understand more than they were able to express for themselves.
  • The researchers found that social skills, measured by a parent reported survey, was a high associated predictor of a person's receptive language ability within this study.
  • Finally, the researchers found that having better motor skills, measured by a developmental coordination disorder survey, was the highest predictor of having a discrepancy between spoken language and understood language. This suggests that the better the motor skills a minimally verbal child or adolescent has, the more they are likely to have better understanding of the language communicated to them.
  • The researchers suggested that the Vineland Adaptive Behavior Score, used as a standard for adaptive behaviors across many studies and within Simons Searchlight, was the most appropriate measure for minimally verbal people compared with some of the other measures used.
  • The researchers suggested that having better motor skills allows children better exposure to different activities and environments, which promotes language development.Show Less
Autism Res Epub ahead of print, (2023)
Chen et al.
Full Article

All Genes
2023

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

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

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

16p11.2 deletion
1q21.1 deletion
ADNP
ASXL3
CHAMP1
CSNK2A1
CTNNB1
DYRK1A
GRIN2B
HIVEP2
PCHD1
PPP2R1A
PPP2R5D
SCN2A
STXBP1
SYNGAP1
2022