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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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.

Show More
Show Less

Search

  • Filter
  • Clear All
Genetic Condition
Year of Publication
108 Publications
Neurodevelopmental phenotypes associated with pathogenic variants in SLC6A1
  • This is the first publication on SLC6A1 that includes Simons Searchlight data.Show More
  • 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.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
J Med Genet 59, 536-543 (2022)
Kahen et al.
Full Article

SLC6A1
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

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

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

DYRK1A
2022

Sensory processing in 16p11.2 deletion and 16p11.2 duplication
  • The 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.Show More
  • 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.
  • These results suggest that a detailed breakdown of sensory processing in people with a 16p11.2 deletion or duplication could be used for clinical evaluations.Show Less
Autism Res 15, 2081-2098 (2022)
Smith et al.
Full Article

16p11.2 deletion
16p11.2 duplication
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

PPP2R5D
2022

ConVnet BiLSTM for ASD classification on EEG brain signal
  • The goal of this research was to develop and validate a new computer-based method to assist doctors in diagnosing autism. The method used a convolutional neural network (ConVnet) structure that merges two LSTM blocks (BiLSTM). This computational deep learning method identifies patterns in electroencephalogram (EEG) information to help with diagnoses. ConVnet BiLSTM has been used with high accuracy in recent research studies on other topics, such as seizure detection or human motor recognition.Show More
  • This study included Simons Searchlight participants with a 16p11.2 deletion or a 16p11.2 duplication, as well as people with no genetic conditions from Boston Children’s Hospital. Participants were age 10 and younger.
  • Using the ConVnet BiLSTM method, the researchers were able to classify participants as autistic in a quick, inexpensive, and noninvasive way. The researchers created a recognizable pattern from participant EEGs. This deep learning method predicted autism with over 97 percent accuracy.
  • The researchers suggested that this method could be used by doctors to assist in the diagnosis of autism as an alternative to the current behavioral criteria from the diagnostic manual.Show Less
iJOE 18, (2022)
Ali et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2022