LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article: Mutational Landscape of Autism Spectrum Disorder Brain Tissue

Woodbury-Smith, Marc / Lamoureux, Sylvia / Begum, Ghausia / Nassir, Nasna / Akter, Hosneara / O’Rielly, Darren D. / Rahman, Proton / Wintle, Richard F. / Scherer, Stephen W. / Uddin, Mohammed

Genes. 2022 Jan. 24, v. 13, no. 2

2022

Abstract: Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism ... ...

Abstract	Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism from peripheral samples. In this study, we undertook whole exome sequencing on brain tissue from 26 ASD brain donors from the Harvard Brain Tissue Resource Center (HBTRC) and ascertained the presence of post-zygotic and germline mutations categorized as pathological, including those impacting known ASD-implicated genes. Although quantification did not reveal enrichment for post-zygotic mutations compared with the controls (n = 15), a small number of pathogenic, potentially ASD-implicated mutations were identified, notably in TRAK1 and CLSTN3. Furthermore, germline mutations were identified in the same tissue samples in several key ASD genes, including PTEN, SC1A, CDH13, and CACNA1C. The establishment of tissue resources that are available to the scientific community will facilitate the discovery of new mutations for ASD and other neurodevelopmental disorders.
Keywords	autism ; brain ; germ cells ; mutation
Language	English
Dates of publication	2022-0124
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13020207
Database	NAL-Catalogue (AGRICOLA)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Disruption of DDX53 coding sequence has limited impact on iPSC-derived human NGN2 neurons.

Faheem, Muhammad / Deneault, Eric / Alexandrova, Roumiana / Rodrigues, Deivid C / Pellecchia, Giovanna / Shum, Carole / Zarrei, Mehdi / Piekna, Alina / Wei, Wei / Howe, Jennifer L / Thiruvahindrapuram, Bhooma / Lamoureux, Sylvia / Ross, P Joel / Bradley, Clarrisa A / Ellis, James / Scherer, Stephen W

BMC medical genomics

2023 Volume 16, Issue 1, Page(s) 5

Abstract: Background: The X-linked PTCHD1 locus is strongly associated with autism spectrum disorder (ASD). Males who carry chromosome microdeletions of PTCHD1 antisense long non-coding RNA (PTCHD1-AS)/DEAD-box helicase 53 (DDX53) have ASD, or a sub-clinical form ...

Abstract	Background: The X-linked PTCHD1 locus is strongly associated with autism spectrum disorder (ASD). Males who carry chromosome microdeletions of PTCHD1 antisense long non-coding RNA (PTCHD1-AS)/DEAD-box helicase 53 (DDX53) have ASD, or a sub-clinical form called Broader Autism Phenotype. If the deletion extends beyond PTCHD1-AS/DDX53 to the next gene, PTCHD1, which is protein-coding, the individuals typically have ASD and intellectual disability (ID). Three male siblings with a 90 kb deletion that affects only PTCHD1-AS (and not including DDX53) have ASD. We performed a functional analysis of DDX53 to examine its role in NGN2 neurons. Methods: We used the clustered regularly interspaced short palindromic repeats (CRISPR) gene editing strategy to knock out DDX53 protein by inserting 3 termination codons (3TCs) into two different induced pluripotent stem cell (iPSC) lines. DDX53 CRISPR-edited iPSCs were differentiated into cortical excitatory neurons by Neurogenin 2 (NGN-2) directed differentiation. The functional differences of DDX53-3TC neurons compared to isogenic control neurons with molecular and electrophysiological approaches were assessed. Results: Isogenic iPSC-derived control neurons exhibited low levels of DDX53 transcripts. Transcriptional analysis revealed the generation of excitatory cortical neurons and DDX53 protein was not detected in iPSC-derived control neurons by western blot. Control lines and DDX53-3TC neurons were active in the multi-electrode array, but no overt electrophysiological phenotype in either isogenic line was observed. Conclusion: DDX53-3TC mutation does not alter NGN2 neuronal function in these experiments, suggesting that synaptic deficits causing ASD are unlikely in this cell type.
MeSH term(s)	Humans ; Male ; Autism Spectrum Disorder/genetics ; DEAD-box RNA Helicases/genetics ; Induced Pluripotent Stem Cells/metabolism ; Mutation ; Neurons/metabolism
Chemical Substances	DDX53 protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2411865-5
ISSN	1755-8794 ; 1755-8794
ISSN (online)	1755-8794
ISSN	1755-8794
DOI	10.1186/s12920-022-01425-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Mutational Landscape of Autism Spectrum Disorder Brain Tissue.

Woodbury-Smith, Marc / Lamoureux, Sylvia / Begum, Ghausia / Nassir, Nasna / Akter, Hosneara / O'Rielly, Darren D / Rahman, Proton / Wintle, Richard F / Scherer, Stephen W / Uddin, Mohammed

Genes

2022 Volume 13, Issue 2

Abstract	Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism from peripheral samples. In this study, we undertook whole exome sequencing on brain tissue from 26 ASD brain donors from the Harvard Brain Tissue Resource Center (HBTRC) and ascertained the presence of post-zygotic and germline mutations categorized as pathological, including those impacting known ASD-implicated genes. Although quantification did not reveal enrichment for post-zygotic mutations compared with the controls (
MeSH term(s)	Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/pathology ; Brain/pathology ; Calcium-Binding Proteins/genetics ; Genetic Predisposition to Disease ; Humans ; Membrane Proteins/genetics ; Mutation ; Whole Exome Sequencing
Chemical Substances	CLSTN3 protein, human ; Calcium-Binding Proteins ; Membrane Proteins
Language	English
Publishing date	2022-01-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13020207
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A novel intronic variant in UBE3A identified by genome sequencing in a patient with an atypical presentation of Angelman syndrome.

Curtis, Meredith / Baribeau, Danielle / Walker, Susan / Carter, Melissa / Costain, Gregory / Lamoureux, Sylvia / Liston, Eriskay / Marshall, Christian R / Reuter, Miriam S / Snell, Meaghan / Summers, Jane / Vorstman, Jacob / Jobling, Rebekah K

American journal of medical genetics. Part A

2020 Volume 182, Issue 9, Page(s) 2145–2151

Abstract: Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10-15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with ...

Abstract	Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10-15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with conventional testing. We describe a 13-year-old male with an atypical presentation of AS, who was found to have a novel, maternally inherited, intronic variant in UBE3A (c.3-12T>A) using genome sequencing (GS). Targeted sequencing of RNA isolated from blood confirmed the creation of a new acceptor splice site. These GS results ended a six-year diagnostic odyssey and revealed a 50% recurrence risk for the unaffected parents. This case illustrates a previously unreported splicing variant causing AS. Intronic variants identifiable by GS may account for a proportion of individuals who are suspected of having well-known genetic disorders despite negative prior genetic testing.
MeSH term(s)	Adolescent ; Alleles ; Angelman Syndrome/genetics ; Angelman Syndrome/pathology ; Child ; Chromosome Mapping ; Genetic Predisposition to Disease ; Genetic Variation/genetics ; Humans ; Introns/genetics ; Male ; Mutation/genetics ; RNA Splice Sites/genetics ; Ubiquitin-Protein Ligases/genetics ; Whole Genome Sequencing/methods
Chemical Substances	RNA Splice Sites ; UBE3A protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2020-07-11
Publishing country	United States
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.61740
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1376/A: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Genome sequencing for detection of pathogenic deep intronic variation: A clinical case report illustrating opportunities and challenges.

Walker, Susan / Lamoureux, Sylvia / Khan, Tayyaba / Joynt, Alyssa C M / Bradley, Melissa / Branson, Helen M / Carter, Melissa T / Hayeems, Robin Z / Jagiello, Lukasz / Marshall, Christian R / Meyn, M Stephen / Miller, Steven P / Wilson, Diane / Scherer, Stephen W / Blaser, Susan / Mireskandari, Kamiar / Costain, Gregory

American journal of medical genetics. Part A

2021 Volume 185, Issue 10, Page(s) 3129–3135

Abstract: Variants in JAM3 have been reported in four families manifesting a severe autosomal recessive disorder characterized by hemorrhagic destruction of the brain, subependymal calcification, and cataracts. We describe a 7-year-old male with a similar ... ...

Abstract	Variants in JAM3 have been reported in four families manifesting a severe autosomal recessive disorder characterized by hemorrhagic destruction of the brain, subependymal calcification, and cataracts. We describe a 7-year-old male with a similar presentation found by research-based quad genome sequencing to have two novel splicing variants in trans in JAM3, including one deep intronic variant (NM_032801.4: c.256+1260G>C) not detectable by standard exome sequencing. Targeted sequencing of RNA isolated from transformed lymphoblastoid cell lines confirmed that each of the two variants has a deleterious effect on JAM3 mRNA splicing. The role for genome sequencing as a clinical diagnostic test extends to those patients with phenotypes strongly suggestive of a specific Mendelian disorder, especially when the causal genetic variant(s) are not found by a more targeted approach. Barriers to diagnosis via identification of pathogenic deep intronic variation include lack of laboratory consensus regarding in silico splicing prediction tools and limited access to clinically validated confirmatory RNA experiments.
MeSH term(s)	Adult ; Brain Diseases/diagnosis ; Brain Diseases/diagnostic imaging ; Brain Diseases/genetics ; Brain Diseases/pathology ; Cell Adhesion Molecules/genetics ; Child ; Female ; Hemorrhagic Disorders/diagnosis ; Hemorrhagic Disorders/diagnostic imaging ; Hemorrhagic Disorders/genetics ; Hemorrhagic Disorders/pathology ; Humans ; Introns/genetics ; Male ; Mutation/genetics ; Pedigree ; Protein Isoforms/genetics ; RNA Splicing/genetics ; Whole Exome Sequencing
Chemical Substances	Cell Adhesion Molecules ; JAM3 protein, human ; Protein Isoforms
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.62389
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1376/A: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Gene copy number variation and pediatric mental health/neurodevelopment in a general population.

Zarrei, Mehdi / Burton, Christie L / Engchuan, Worrawat / Higginbotham, Edward J / Wei, John / Shaikh, Sabah / Roslin, Nicole M / MacDonald, Jeffrey R / Pellecchia, Giovanna / Nalpathamkalam, Thomas / Lamoureux, Sylvia / Manshaei, Roozbeh / Howe, Jennifer / Trost, Brett / Thiruvahindrapuram, Bhooma / Marshall, Christian R / Yuen, Ryan K C / Wintle, Richard F / Strug, Lisa J /

Stavropoulos, Dimitri J / Vorstman, Jacob A S / Arnold, Paul / Merico, Daniele / Woodbury-Smith, Marc / Crosbie, Jennifer / Schachar, Russell J / Scherer, Stephen W

Human molecular genetics

2023 Volume 32, Issue 15, Page(s) 2411–2421

Abstract: We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit ... ...

Abstract	We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit for Science). Clinically significant or susceptibility CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of attention-deficit/hyperactivity disorder (ADHD) traits (P = 5.0 × 10-3), longer response inhibition (a cognitive deficit found in several mental health and neurodevelopmental disorders; P = 1.0 × 10-2) and increased prevalence of mental health diagnoses (P = 1.9 × 10-6, odds ratio: 3.09), specifically ADHD, autism spectrum disorder anxiety and learning problems/learning disorder (P's < 0.01). There was an increased burden of rare deletions in gene-sets related to brain function or expression in brain associated with more ADHD traits. With the current mental health crisis, our data established a baseline for delineating genetic contributors in pediatric-onset conditions.
MeSH term(s)	Adolescent ; Humans ; Child ; Mental Health ; DNA Copy Number Variations/genetics ; Autism Spectrum Disorder/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Attention Deficit Disorder with Hyperactivity/epidemiology ; Attention Deficit Disorder with Hyperactivity/genetics ; Gene Dosage
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddad074
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3469: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Copy number variation in fetal alcohol spectrum disorder.

Zarrei, Mehdi / Hicks, Geoffrey G / Reynolds, James N / Thiruvahindrapuram, Bhooma / Engchuan, Worrawat / Pind, Molly / Lamoureux, Sylvia / Wei, John / Wang, Zhouzhi / Marshall, Christian R / Wintle, Richard F / Chudley, Albert E / Scherer, Stephen W

Biochemistry and cell biology = Biochimie et biologie cellulaire

2018 Volume 96, Issue 2, Page(s) 161–166

Abstract: Fetal alcohol spectrum disorder (FASD) is characterized by a combination of neurological, developmental, and congenital defects that may occur as a consequence of prenatal alcohol exposure. Earlier reports showed that large chromosomal anomalies may link ...

Abstract	Fetal alcohol spectrum disorder (FASD) is characterized by a combination of neurological, developmental, and congenital defects that may occur as a consequence of prenatal alcohol exposure. Earlier reports showed that large chromosomal anomalies may link to FASD. Here, we examined the prevalence and types of copy number variations (CNVs) in FASD cases previously diagnosed by a multidisciplinary FASD team in sites across Canada. We genotyped 95 children with FASD and 87 age-matched, typically developing controls on the Illumina Human Omni2.5 SNP (single nucleotide polymorphisms) array platform. We compared their CNVs with those of 10 851 population controls to identify rare CNVs (<0.1% frequency), which may include large unbalanced chromosomal abnormalities, that might be relevant to FASD. In 12/95 (13%) of the FASD cases, rare CNVs were found that impact potentially clinically relevant developmental genes, including the CACNA1H involved in epilepsy and autism, the 3q29 deletion disorder, and others. Our results show that a subset of children diagnosed with FASD have chromosomal deletions and duplications that may co-occur or explain the neurodevelopmental impairments in a diagnosed cohort of FASD individuals. Children suspected to have FASD with or without sentinel facial features of fetal alcohol syndrome and neurodevelopmental delays should potentially be evaluated by a clinical geneticist and possibly have genetic investigations as appropriate to exclude other etiologies.
MeSH term(s)	Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 3/genetics ; Female ; Fetal Alcohol Spectrum Disorders/genetics ; Gene Dosage ; Humans ; Male ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2018-03-13
Publishing country	Canada
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	54104-7
ISSN	1208-6002 ; 0829-8211
ISSN (online)	1208-6002
ISSN	0829-8211
DOI	10.1139/bcb-2017-0241
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.206: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder.

Chan, Ada J S / Engchuan, Worrawat / Reuter, Miriam S / Wang, Zhuozhi / Thiruvahindrapuram, Bhooma / Trost, Brett / Nalpathamkalam, Thomas / Negrijn, Carol / Lamoureux, Sylvia / Pellecchia, Giovanna / Patel, Rohan V / Sung, Wilson W L / MacDonald, Jeffrey R / Howe, Jennifer L / Vorstman, Jacob / Sondheimer, Neal / Takahashi, Nicole / Miles, Judith H / Anagnostou, Evdokia /

Tammimies, Kristiina / Zarrei, Mehdi / Merico, Daniele / Stavropoulos, Dimitri J / Yuen, Ryan K C / Fernandez, Bridget A / Scherer, Stephen W

Nature communications

2022 Volume 13, Issue 1, Page(s) 6463

Abstract: Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and ... ...

Abstract	Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We develop a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD have a significantly higher GRVS compared to those with nondysmorphic ASD (P = 0.03). Using the polygenic transmission disequilibrium test, we observe an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P = 2.9 × 10
MeSH term(s)	Child ; Humans ; Autism Spectrum Disorder/genetics ; Canada/epidemiology ; Genome ; Multifactorial Inheritance/genetics ; Whole Genome Sequencing ; Genetic Predisposition to Disease
Language	English
Publishing date	2022-10-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34112-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

Fehlings, Darcy L / Zarrei, Mehdi / Engchuan, Worrawat / Sondheimer, Neal / Thiruvahindrapuram, Bhooma / MacDonald, Jeffrey R / Higginbotham, Edward J / Thapa, Ritesh / Behlim, Tarannum / Aimola, Sabrina / Switzer, Lauren / Ng, Pamela / Wei, John / Danthi, Prakroothi S / Pellecchia, Giovanna / Lamoureux, Sylvia / Ho, Karen / Pereira, Sergio L / de Rijke, Jill /

Sung, Wilson W L / Mowjoodi, Alireza / Howe, Jennifer L / Nalpathamkalam, Thomas / Manshaei, Roozbeh / Ghaffari, Siavash / Whitney, Joseph / Patel, Rohan V / Hamdan, Omar / Shaath, Rulan / Trost, Brett / Knights, Shannon / Samdup, Dawa / McCormick, Anna / Hunt, Carolyn / Kirton, Adam / Kawamura, Anne / Mesterman, Ronit / Gorter, Jan Willem / Dlamini, Nomazulu / Merico, Daniele / Hilali, Murto / Hirschfeld, Kyle / Grover, Kritika / Bautista, Nelson X / Han, Kara / Marshall, Christian R / Yuen, Ryan K C / Subbarao, Padmaja / Azad, Meghan B / Turvey, Stuart E / Mandhane, Piush / Moraes, Theo J / Simons, Elinor / Maxwell, George / Shevell, Michael / Costain, Gregory / Michaud, Jacques L / Hamdan, Fadi F / Gauthier, Julie / Uguen, Kevin / Stavropoulos, Dimitri J / Wintle, Richard F / Oskoui, Maryam / Scherer, Stephen W

Nature genetics

2024 Volume 56, Issue 4, Page(s) 585–594

Abstract: We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of ... ...

Abstract	We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.
MeSH term(s)	Humans ; Child ; DNA Copy Number Variations/genetics ; Cerebral Palsy/genetics ; Mutation ; Whole Genome Sequencing ; Genomics
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-024-01686-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Germline and somatic mutations in

Uddin, Mohammed / Woodbury-Smith, Marc / Chan, Ada / Brunga, Ledia / Lamoureux, Sylvia / Pellecchia, Giovanna / Yuen, Ryan K C / Faheem, Muhammad / Stavropoulos, Dimitri J / Drake, James / Hahn, Cecil D / Hawkins, Cynthia / Shlien, Adam / Marshall, Christian R / Turner, Lesley A / Minassian, Berge A / Scherer, Stephen W / Boelman, Cyrus

Neurology. Genetics

2017 Volume 3, Issue 6, Page(s) e199

Abstract: Objective: To expand the clinical phenotype associated with : Methods: Patients with : Results: Seven patients with heterozygous de novo mutations affecting the coding region of : Conclusions: ... ...

Abstract	Objective: To expand the clinical phenotype associated with Methods: Patients with Results: Seven patients with heterozygous de novo mutations affecting the coding region of Conclusions: STXBP1
Language	English
Publishing date	2017-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000000199
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito