Publications

 

Below is the list of published research papers that were made possible through the Simons Searchlight research registry. Thank you to all the families for participating in Simons Searchlight. Our long-term goal is to continue to help researchers and leading geneticists from around the world learn about you or your family’s genetic disorders.

We summarized the overall points and main findings of the research articles, although you can click on the link “Full Article” if you would like to see the original paper.

You will notice, that there are many papers that include the name, Simons Variation in Individuals Project or SimonsVIP. This is because Simons Searchlight was originally called SimonsVIP and they are one and the same research program.

We have listed the articles in order of date, from oldest to newest. Please click on the categories below to look for publications on specific genetic conditions. As of January 2023, Simons Searchlight resources have been used in 84 publications and preprints, we will continue to summarize publications as they come out. 

How to read the publication reference titles:

After the title of the article, we include other details about where the article was published and the year it was written. If there were more than 3 authors, the words “et al” are used instead of listing all the authors. “Et al” means “and others.” The name of the journal is written in shorthand.

Disclaimer: Please note, papers in medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive), are not peer-reviewed or edited before being posted online. All other articles in journals listed here have been reviewed by other researchers for quality control. When a paper is posted on medRxiv or bioRxiv, the researchers are able to make their findings available right away to the medical and scientific community. However, because they have not been reviewed by other researchers, the final results might look a little different once they are officially published in a journal.

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Genetic Condition
Year of Publication
84 Publications
Rare CNVs and phenome-wide profiling: A tale of brain-structural divergence and phenotypical convergence
  • These researchers compared the brain structures of people with copy number variants (CNVs) and people in the UK Biobank that were from the general population. This study included eight CNVs: deletions or duplications of 1q21.1, 15p11.2, 16p11.2, and 22q11.2.Show More
  • This study included participants from several research studies or universities: Simons Searchlight; Cardiff University; 16p11.2 European Consortium; University of Montreal; and University of California, Los Angeles. There were 548 people with a CNV and 312 people with no genetic condition.
  • The researchers used computer analytics to study the brain features of each of the CNVs and created one of the largest brain imaging studies to date.
  • They made a comparison between brain structures and medical features in order to find links between the two. They aimed to understand how brain structure can lead to behaviors.
  • Brain volumes were smaller for participants with a 1q21.1 deletion, 15p11.2 duplication, 16p11.2 duplication, and 22q11.2 deletion. Brain volumes were bigger for people with a 1q21.1 duplication, 15p11.2 deletion, 16p11.2 deletion, and 22q11.2 duplication.
  • They found that people with a 16p11.2 deletion or 22q11.2 deletion had unique brain patterns, whereas people with a 15p11.2 duplication had brain structures that were similar to the general population.
  • People with a 16p11.2 deletion had the largest number of brain regions affected, whereas people with a 15p11.2 duplication had the lowest number of regions affected.
  • The researchers created a graph showing the large-scale network of each CNV, and they studied other characteristics of people with a CNV, such as body size, lifestyle, and blood factors. All eight CNVs had strong associations with diastolic blood pressure, alkaline phosphatase, and red blood cell count.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
bioRxiv Preprint, (2022)
Kopal et al.
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.
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.
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.
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.
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.
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.