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 90 publications and preprints, we will continue to summarize publications as they come out. 

The Simons Foundation encourages researchers to make publications free to the public, also called open access. If you are unable to access the official journal articles, we recommend that you contact the author listed last on the article to request a copy.

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Disclaimer: Please note, papers in medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive), are not peer-reviewed or edited before being posted online.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.

Show More
Show Less

Search

  • Filters
  • Clear All
Genetic Condition
Year of Publication
90 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

Tags:

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

Tags:

16p11.2 deletion
All Genes
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

Tags:

All Genes
CSNK2A1
DYRK1A
PPP2R5D
2023
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

Tags:

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 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, such as 16p11.2, had more structural changes on the MRI. All 11 CNVs had changes in the thickness of the brain region that affects cognitive, affective, and social functions. The large effects were seen in participants with a 16p11.2 or 1q21.1 CNVs.
  • 16p11.2 duplications had brain structure changes that were different than those seen in people with ASD and people with no genetic diagnosis. This suggests that there may be several different brain changes that may lead to autism.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
medRxiv Preprint, (2023)
Kumar et al.
Full Article

Tags:

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

Tags:

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

Tags:

HIVEP2
2022
en English
af Afrikaanssq Albanianam Amharicar Arabichy Armenianaz Azerbaijanieu Basquebe Belarusianbn Bengalibs Bosnianbg Bulgarianca Catalanceb Cebuanony Chichewazh-CN Chinese (Simplified)zh-TW Chinese (Traditional)co Corsicanhr Croatiancs Czechda Danishnl Dutchen Englisheo Esperantoet Estoniantl Filipinofi Finnishfr Frenchfy Frisiangl Galicianka Georgiande Germanel Greekgu Gujaratiht Haitian Creoleha Hausahaw Hawaiianiw Hebrewhi Hindihmn Hmonghu Hungarianis Icelandicig Igboid Indonesianga Irishit Italianja Japanesejw Javanesekn Kannadakk Kazakhkm Khmerko Koreanku Kurdish (Kurmanji)ky Kyrgyzlo Laola Latinlv Latvianlt Lithuanianlb Luxembourgishmk Macedonianmg Malagasyms Malayml Malayalammt Maltesemi Maorimr Marathimn Mongolianmy Myanmar (Burmese)ne Nepalino Norwegianps Pashtofa Persianpl Polishpt Portuguesepa Punjabiro Romanianru Russiansm Samoangd Scottish Gaelicsr Serbianst Sesothosn Shonasd Sindhisi Sinhalask Slovaksl Slovenianso Somalies Spanishsu Sudanesesw Swahilisv Swedishtg Tajikta Tamilte Teluguth Thaitr Turkishuk Ukrainianur Urduuz Uzbekvi Vietnamesecy Welshxh Xhosayi Yiddishyo Yorubazu Zulu