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Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication.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
SETBP1 haploinsufficiency and related disorders clinical and neurobehavioral phenotype study
  • This study used Simons Searchlight genetic, behavioral, and clinical data to describe the neurodevelopmental profile and clinical characteristics of people with genetic variants that cause SETBP1 haploinsufficiency disorder (SETBP1-HD) and SETBP1 related disorders (SETBP1-RD). SETBP1 variants associated with Schinzel-Giedion syndrome in the specific amino acid region of SETBP1 862-873 were not included in this analysis.Show More
  • The researchers studied 34 Simons Searchlight participants, including 28 with SETBP1-HD and 6 with SETBP1-RD.
  • The publication included a review of medical history, Vineland Adaptive Behavior Scales 3 (VABS-3), Child Behavior Checklist (CBCL), Social Responsiveness Scale (SRS-2), Social Communication Questionnaire (SCQ), Children’s Sleep Habits Questionnaire (CSHQ), sleep surveys, brief development update, and Background History Form.
  • This is the first study in which researchers compared the medical features of people with SETBP1-HD and SETBP1-RD.
  • The researchers found that there were clinical features in common between participants with SETBP1-HD and SETBP1-RD, such as intellectual disability and developmental delay, speech and language impairment, hypotonia, attention issues, gastrointestinal issues, vision issues, sleep issues, autistic traits, and high pain tolerance.
  • The researchers thought that participants with SETBP1-RD had more heart and orthopedic issues, as well as difficulty in bowel control and higher risks for somatic issues, than participants with SETBP1-HD.
  • Participants with SETBP1-HD were better with interpersonal relationships, but had more difficulty with communication, motor skills, and functioning safely and independently within the community, according to the VABS-3.
  • As participants got older, new challenges arose. Participants with SETBP1-RD tended to develop more restrictive and repetitive behaviors. Participants with SETBP1-HD had an increase in overall behavioral and emotional problems.Show Less
Clin Genet Epub ahead of print, (2024)
Oyler et al.
Full Article

SETBP1
2024

Challenges in multi-task learning for fMRI-based diagnosis: Benefits for psychiatric conditions and CNVs would likely require thousands of patients
  • The researchers aimed to use computer machine learning to see if it is possible to detect and diagnose certain genetic conditions from brain imaging. They collected resting-state functional magnetic resonance imaging (rs-fMRI) data for 7 different copy number variants.Show More
  • Imaging data from Simons Searchlight participants with a 16p11.2 deletion, 16p11.2 duplication, 1q21.1 deletion, and 1q21.1 duplication were included in this research, as well as data from other research studies.
  • rs-fMRI images from 2,872 individuals were included from people with a 1q21.1 deletion, 1q21.1 duplication, 15q11.2 deletion, 16p11.2 deletion, 16p11.2 duplication, 22q11.2 deletion, and 22q11.2 duplication. These images were compared to images from people with no genetic diagnosis. The researchers also obtained images from people diagnosed with attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, and bipolar disorder.
  • Once the researchers completed the machine learning process, they compared their results with images from the UK Biobank, which contains data from 30,185 people.
  • The researchers described the method used, called multi-task learning, and how they applied it to the various image datasets.
  • The researchers found that overall, multi-task learning might be a possible predictor of the sex and age of a person with no genetic diagnosis in the UK Biobank.
  • The researchers found that it was difficult to use machine learning to diagnose ADHD, autism, schizophrenia, bipolar disorder, or any of the copy number variants tested in this study. 22q11.2 deletion had the highest accuracy (about 90 percent), whereas schizophrenia, bipolar disorder, 16p11.2 deletion, 16p11.2 duplication, and 1q21.1 deletion reached over 70 percent accuracy, in one particular model tested. The findings were not always consistent in the other types of machine learning models.
  • The researchers indicated that the sample size of the image set used for machine learning was a very important factor for detecting a diagnosis correctly. Show Less
Imaging Neurosci 2, 1-20 (2024)
Harvey et al.
Full Article

16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
2024

MED13L-related disorder characterized by severe motor speech impairment
  • The researchers looked at the speech, language, motor, cognitive, adaptive, and behavioral features of Simons Searchlight participants with MED13L-related syndrome. They also included in-person research data collected in 2022 at a MED13L Family and Research Conference. Show More
  • This study included 17 people from the in-person assessment and 67 online participants with likely pathogenic and pathogenic MED13L variants.
  • Everyone from the in-person assessment had a motor speech disorder, such as childhood apraxia of speech, dysarthria, or both. Childhood apraxia of speech is a speech disorder caused by a problem with communication between the brain and the muscles used for speaking. Dysarthria is a speech disorder that results when the muscles used to speak become paralyzed or weakened. Everyone had severe impairment in receptive language (ability to understand language) and expressive language (ability to express yourself).
  • Most Simons Searchlight participants with MED13L-related syndrome reported having a language disorder (65 out of 67 people). One out of 3 children were minimally verbal or non-verbal after the age of 4.
  • In-person assessment of gross and fine motor deficits were comparable to what was reported online.
  • Motor speech disorders were common in the study participants, and this was considered to be consistent with a muscular/mechanical defect rather than a purely cognitive defect.
  • The researchers also suggested that there might be a higher rate of germline mosaicism in the MED13L community. Germline mosaic is when a person’s egg cells or sperm cells carry the same genetic variant, but that person does not have that variant detected in blood.Show Less
Research Square Preprint, (2024)
Mitchel et al.
Full Article

MED13L
2024

A comparison of symptom profiles in probands with 16p11.2 deletion and duplication syndromes: Repetitive behavior and psychosis proneness
  • Simons Searchlight data was used at Bucknell University in an honors thesis.Show More
  • The student looked at repetitive behavior and psychosis spectrum behavior in 116 people with a 16p11.2 deletion and 59 people with a 16p11.2 duplication. The study also included 32 people with no genetic diagnosis.
  • The student used information from 3 surveys: the Childhood Routines Inventory-Revised, the Childhood Oxford-Liverpool Inventory of Feelings and Experiences, and the Child Behavior Checklist.
  • The student found that, in general, people with a 16p11.2 duplication had more severe maladaptive repetitive behaviors and psychosis symptoms than people with a 16p11.2 deletion.
  • People with a 16p11.2 duplication more often had repetitive, compulsive-like behaviors and were prone to psychosis.
  • People with a 16p11.2 deletion had more issues with socializing, which was suggested to be a sign of autism in this group.
  • Finally, males with a 16p11.2 duplication were more affected on these surveys compared with females who had a 16p11.2 duplication. No differences were found between males and females with a 16p11.2 deletion.
  • Simons Searchlight is excited that these data are being used by young researchers, perhaps inspiring them to do more research on neurodevelopmental conditions. Show Less
Bucknell University, Honors Theses 686, (2024)
Rakauskas
Full Article

16p11.2 deletion
16p11.2 duplication
2024

Rare CNVs and phenome-wide profiling highlight 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 in participants with a 1q21.1 deletion, 15p11.2 duplication, 16p11.2 duplication, and 22q11.2 deletion. Brain volumes were bigger in 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 highest 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 characteristics of people with a CNV, such as body size, lifestyle, and blood factors. All eight CNVs had strong associations with diastolic blood pressure, a protein called alkaline phosphatase, and red blood cell count.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Nat Hum Behav Epub ahead of print, (2023)
Kopal et al.
Full Article

16p11.2 deletion
16p11.2 duplication
1q21 deletion
1q21 duplication
2023

Subcortical brain alterations in carriers of genomic copy number variants
  • Researchers know that copy number variants (CNV) can contribute to neurodevelopmental and psychiatric disorders, such as autism and schizophrenia. 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 goal of this study was to compare the sizes and patterns of regions of the brain for 11 different CNVs.
  • The researchers studied the following deletions and duplications: 1q21.1, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2. They also studied duplications within chromosome 1, including the TAR region. This study included 675 participants. Brain MRI images for 1q21.1 and 16p11.2 CNVs came from Simons Searchlight participants.
  • The researchers found that CNVs with more genes deleted or duplicated within that region, such as 16p11.2, resulted in more structural changes on magnetic resonance imaging (MRI). All 11 CNVs had changes in the thickness of the brain region that affects cognitive, affective, and social functions. The researchers did not find a link between overall brain volume and the cognition of the person with these CNVs, but, the shape/structure of the brain regions were linked to a person’s cognition.
  • People with 16p11.2 duplications had brain structure changes that were different than those seen in people with autism, and people with no genetic diagnosis. This suggests that there may be several different brain changes that could lead to autism.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Am J Psychiatry 180, 685-698 (2023)
Kumar et al.
Full Article

16p11.2 deletion
16p11.2 duplication
16p13.11 deletion
1q21.1 deletion
1q21.1 duplication
2023

Caregiver-reported dental manifestations in individuals with genetic neurodevelopmental disorders
  • Children with neurodevelopmental disorders (NDDs) are more likely to have dental health issues than children without an NDD. Often these dental hygiene issues are due to a lack of cooperation during brushing or dental visits.Show More
  • To learn whether people with NDDs have unique dental issues, the researchers surveyed Simons Searchlight caregivers to ask about dental features found in their dependents. This question was raised by a parent in a Simons Searchlight community.
  • The researchers studied 39 genetic conditions, which included 620 people with a genetic NDD, and they compared the findings with those of 145 siblings with no genetic finding.
  • In general, people within the NDD group had more issues with drooling, late first teeth appearance, and abnormal shape of first and second teeth.
  • This is the first time that researchers found genetic variations in CSNK2A1, DYRK1A, and PPP2R5D were each associated with specific dental features.
  • About half of children with a CSNK2A1-related NDD had defects in their first teeth, such as longer than average front teeth, cracked teeth, missing enamel, small teeth, or fused teeth.
  • About half of children with a damaging DYRK1A genetic variant had delayed appearance of the first teeth.
  • Finally, about 2 out of 3 children with a pathogenic PPP2R5D genetic variant had excessive drooling.Show Less
Int J Paediatr Dent Epub ahead of print, (2023)
Ming et al.
Full Article

All Genes
CSNK2A1
DYRK1A
PPP2R5D
2023