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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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
Neurodevelopmental phenotypes associated with pathogenic variants in SLC6A1
  • Show MoreThis is the first publication on SLC6A1 that includes Simons Searchlight data.
  • SLC6A1 stands for solute carrier 6 family member 1, and it is important for brain cells to receive signals from other brain cells. Changes in the SLC6A1 gene commonly result in a person having seizures. The most common seizures are absence seizures.
  • The researchers studied 28 Simons Searchlight participants with a pathogenic or likely pathogenic genetic variant in SLC6A1. This adds to the 116 people with SLC6A1 genetic variants that have been published to date in the medical literature.
  • In this study, most of the genetic variants were de novo, which is a random change that happens in the child. But, some of the genetic variants were inherited from a parent.
  • Most participants had seizures, low muscle tone, language problems or speech delay, intellectual disability or developmental delay, and issues with gross motor skills.
  • Less common medical features in the participants included autism, movement disorders, sleep issues, and a high pain tolerance.
  • Show LessThis research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).
J Med Genet 59, 536-543 (2022)
Kahen et al.
Full Article

SLC6A1
2022

Identifying cell type specific driver genes in autism-associated copy number loci from cerebral organoids
  • Show MoreThe 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.
  • 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.
  • Show LessThis research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).
Nat Commun 13, 3243 (2022)
Lim et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2022

Neurodevelopmental profile of HIVEP2-related disorder
  • Show MoreThis is the first publication on HIVEP2 that includes Simons Searchlight data.
  • 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.
  • Show LessThis research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).
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
  • Show MoreChildren 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.
  • 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.
  • Show LessThis research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).
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

Contrastive machine learning reveals the structure of neuroanatomical variation within autism
  • Show MoreThese 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.
  • 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.
  • Show LessThis research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).
Science 376, 1070-1074 (2022)
Aglinskas et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2022

Consistency of parent-report SLC6A1 data in Simons Searchlight with provider-based publications
  • Show MoreTo 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.
  • 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.
  • Show LessThe 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.
J Neurodev Disord 14, 40 (2022)
Bain et al.
Full Article

SLC6A1
2022

Sensory processing in 16p11.2 deletion and 16p11.2 duplication
  • Show MoreThe researchers aimed to understand how people with a 16p11.2 copy number variant (CNV) process sensory information. 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.
  • This study included 38 children with a 16p11.2 deletion, 31 children with a 16p11.2 duplication, and participants from the Simons Searchlight registry.
  • Challenges with sensory processing are common for people with autism. This includes having difficulty with stimulation from the senses, such as light, texture, taste, and sound.
  • Participants with either a 16p11.2 deletion or a 16p11.2 duplication were more likely to have sensory processing challenges than participants without a 16p11.2 deletion or duplication. The sensory processing challenges for participants with a 16p11.2 deletion or duplication were comparable to the sensory processing challenges for participants with autism.
  • Participants with a 16p11.2 deletion or duplication were most likely to have issues with registering sensory information. Participants with a 16p11.2 duplication were more likely to be sensitive to sensory information. Other patterns of sensory processing, such as seeking and avoiding sensory information, were not as common in these two groups.
  • Participants with a 16p11.2 deletion or duplication and autism were more likely to have issues with touch and oral sensations than participants who did not have autism.
  • Show LessThese results suggest that a detailed breakdown of sensory processing in people with a 16p11.2 deletion or duplication could be used for clinical evaluations.
Autism Res 15, 2081-2098 (2022)
Smith et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2022