scholarly journals Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways

2016 ◽  
Vol 6 (3) ◽  
pp. e764-e764 ◽  
Author(s):  
C Cappi ◽  
H Brentani ◽  
L Lima ◽  
S J Sanders ◽  
G Zai ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Obsessive Compulsive Disorder ◽  
Whole Exome Sequencing ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Rare Mutations ◽  
Whole Exome

scholarly journals De novo damaging coding mutations are strongly associated with obsessive-compulsive disorder and overlap with autism

2017 ◽  
Author(s):  
Carolina Cappi ◽  
Melody E. Oliphant ◽  
Zsanett Péter ◽  
Gwyneth Zai ◽  
Catherine A. W. Sullivan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Obsessive Compulsive Disorder ◽  
Whole Exome Sequencing ◽  
Strong Evidence ◽  
De Novo ◽  
High Confidence ◽  
Obsessive Compulsive ◽  
Risk Genes ◽  
Compulsive Disorder ◽  
Whole Exome

ABSTRACTObsessive-compulsive disorder (OCD) is a debilitating developmental neuropsychiatric disorder with a genetic risk component, yet identification of high-confidence risk genes has been challenging. We performed whole-exome sequencing in 222 OCD parent-child trios (184 trios after quality control), finding strong evidence that de novo likely gene disrupting and predicted damaging missense variants contribute to OCD risk. Together, these de novo damaging variants are enriched in OCD probands (RR 1.52, p=0.0005). We identified two high-confidence risk genes, each containing two de novo damaging variants in unrelated probands: CHD8 (Chromodomain Helicase DNA Binding Protein 8) and SCUBE1 (Signal Peptide, CUB Domain And EGF Like Domain Containing 1). Based on our data, we estimate that 34% of de novo damaging variants seen in OCD contribute to risk, and that de novo damaging variants in approximately 335 genes contribute to risk in 22% of OCD cases. Furthermore, genes harboring de novo damaging variants in OCD are enriched for those reported in neurodevelopmental disorders, particularly autism spectrum disorders. An exploratory network analysis reveals significant functional connectivity and enrichment in canonical pathways related to immune response.SIGNIFICANCE STATEMENTDecades of genetic studies in obsessive-compulsive disorder (OCD) have yet to provide reproducible, statistically significant findings. Following an approach that has led to tremendous success in gene discovery for several neuropsychiatric disorders, here we report findings from DNA whole-exome sequencing of patients with OCD and their parents. We find strong evidence for the contribution of spontaneous, or de novo, predicted-damaging genetic variants to OCD risk, identify two high-confidence risk genes, and detect significant overlap with genes previously identified in autism. These results change the status quo of OCD genetics by identifying novel OCD risk genes, clarifying the genetic landscape of OCD with respect to de novo variation, and suggesting underlying biological pathways that will improve our understanding of OCD biology.

Exome sequencing in obsessive–compulsive disorder reveals a burden of rare damaging coding variants

2021 ◽  
Author(s):  
Mathew Halvorsen ◽  
Jack Samuels ◽  
Ying Wang ◽  
Benjamin D. Greenberg ◽  
Abby J. Fyer ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Obsessive Compulsive Disorder ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Coding Variants

scholarly journals Whole Exome Sequencing in Idiopathic Short Stature: rare mutations affecting growth

2019 ◽  
Author(s):  
Shahab Noorian ◽  
Farzaneh Rohani ◽  
Shahram Savad ◽  
Kourosh Kabir ◽  
Nami Mohammadian Khonsari ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Disorders ◽  
Correct Diagnosis ◽  
Test Results ◽  
Rare Mutations ◽  
Whole Exome ◽  
Common Causes ◽  
Blood Specimens

Abstract Introduction: one of the most common causes of referrals to paediatricians is short stature (ISS), some pathogenic mutations may present exactly similar to non-pathogenic causes, our goal is to identify and treat these patients labelled ISS with these mutations and hopefully treat them correctly. Materials and Methods: We assessed All children under the age of fifteen years labelled as ISS. Fourteen of them were confirmed to be ISS and thus were allowed in our study. Afterwards, we pooled their blood specimens and ordered a whole-exome sequencing (WES) test. Results: five patient had normal WES results. Four patients had rare motions that were not studied in the previous literature but due to the functions of the genes, and our patients’ phenotypes it is highly possible that these mutations caused our patients’ short stature. Four patients had known genetic mutations causing short stature. One patient had a mutation with no effect on height. With the help of WES, some rare mutations were found, with the patients’ phenotype and evaluation we identified their function, we diagnosed some other patients’ rare genetic disorders and assessed the possible effect of their mutation on their height and phenotype we aimed to determine how many children labelled as ISS are correctly diagnosed. By WES most of our patient achieved the correct diagnosis which would be impossible to diagnose without WES; thus the reason for their short stature was identified, with the correct diagnosis now we can aim for the proper treatment.

scholarly journals Whole Exome Sequencing in Idiopathic Short Stature: Rare Mutations Affecting Growth

2020 ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Shahab Noorian ◽  
Farzaneh Rohani ◽  
Sharham Savad ◽  
Kourosh Kabir ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Correct Diagnosis ◽  
Idiopathic Short Stature ◽  
Genetic Mutations ◽  
The Past ◽  
Rare Mutations ◽  
Whole Exome ◽  
Directing Attention

Abstract Introduction Evaluation of short stature is a challenge for pediatricians and in the process, idiopathic short stature (ISS) is an often diagnosis of exclusion. Non-pathogenetic mutations affecting height may present with phenotypes similar to the pathogenetic mutations. In this study, we aim to identify the underlying genetic cause of short stature in patients diagnosed with ISS and investigate potential treatments for them. Materials and Methods We identified 14 children in our practice who were under the age of 15 and were initially labelled as ISS. Then, we evaluated their plasma whole-exome sequencing (WES). Results Out of the 14 patients assessed with WES, five had normal results and correctly diagnosed with ISS. However, four of them had rare mutations that have not been extensively studied in the past. Due to the functions of these mutated genes and our patients’ phenotypes, we suspect that these mutations played a role in the short stature. Out of the remaining five patients, four had genetic mutations known to cause short stature and one had a mutation that was known not to affect height. Conclusion In patients who are initially diagnosed with ISS, WES can help to identify rare mutations that may play a role in short stature. Directing attention to these genes, may help with the correct diagnosis and choosing proper treatment for the patients.

scholarly journals Whole-Exome Sequencing in Idiopathic Short Stature: Rare Mutations Affecting Growth

2020 ◽  
Author(s):  
Shahab Noorian ◽  
Nami Mohammadian Khonsari ◽  
Shahram Savad ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Treatment Options ◽  
Idiopathic Short Stature ◽  
Genetic Causes ◽  
Rare Mutations ◽  
Whole Exome ◽  
Common Diagnosis

AbstractIdiopathic short stature (ISS) is a common diagnosis of exclusion in patients with short stature (SS). We aimed to identify the genetic causes of SS in patients with ISS and investigate treatment options. Fourteen children with diagnosis of ISS were identified, and whole-exome sequencing (WES) was subsequently conducted on blood-derived DNA. Five patients were correctly diagnosed with ISS and four had rare mutations that have not been previously reported. Four patients had mutations known to cause SS and one had a mutation that was known not to affect height. WES can help identify rare mutations implicated in ISS.

scholarly journals PCR-free whole exome sequencing: Cost-effective and efficient in detecting rare mutations

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222562
Author(s):  
Izumi Yamaguchi ◽  
Takashi Watanabe ◽  
Osamu Ohara ◽  
Yoshinori Hasegawa
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Cost Effective ◽  
Rare Mutations ◽  
Whole Exome ◽  
Sequencing Cost

scholarly journals Correction: Whole-Exome Sequencing Efficiently Detects Rare Mutations in Autosomal Recessive Nonsyndromic Hearing Loss

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
Author(s):  
Oscar Diaz-Horta ◽  
Duygu Duman ◽  
Joseph Foster ◽  
Aslı Sırmacı ◽  
Michael Gonzalez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Nonsyndromic Hearing Loss ◽  
Rare Mutations ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing Efficiently Detects Rare Mutations in Autosomal Recessive Nonsyndromic Hearing Loss

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50628 ◽  
Author(s):  
Oscar Diaz-Horta ◽  
Duygu Duman ◽  
Joseph Foster ◽  
Aslı Sırmacı ◽  
Michael Gonzalez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Nonsyndromic Hearing Loss ◽  
Rare Mutations ◽  
Whole Exome
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