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  • 1
    Article
    Article
    Autosomal dominant intellectual disability
    2018
    ISSN: 0936-5931 
    Details
    Language: English
    In: Medizinische Genetik, 2018-10-11, Vol.30 (3), p.318-322
    Description: Intellectual disability (ID) is a heterogeneous entity defined as a substantial impairment of cognitive and adaptive function with an onset in early childhood and an IQ measure of less than 70. During the last few years, the next generation technologies, namely whole exome (WES) and whole genome sequencing (WGS), have given rise to the identification of many new genes for autosomal dominant (ADID), autosomal recessive (ARID) and X‑linked forms of ID (XLID). The prevalence of ID is 1.5–2% for milder forms (IQ 〈 70) and 0.3–0.5% for more severe forms of ID (IQ 〈 50). Up to now, about 650 genes for ADID have been reported and it is expected that there are at least 350 genes still unidentified. Although the ADID genes can easily be classified according to the associated clinical findings, e. g. different kind of seizures, abnormal body measurements, an advanced selection of reasonable genes for analyses is challenging. Many different panels for ID genes have been developed for a first diagnostic step, but more meaningful is the use of trio exome sequencing in individuals with sporadic ID. Using trio WES the mutation detection rate for de novo mutations in ID varies from 20 to 60%. Further research is needed for the identification of the remaining ID genes, a deeply understanding of the pathways and the development of therapies for the mostly rare causes of ID.
    Subject(s): Autosomal dominant ; Body measurements ; Children ; Cognitive ability ; De novo ; Geistige Behinderung ; Gene Therapy ; general ; Genomes ; Gynecology ; Hochdurchsatz-Sequenzierung ; Human Genetics ; Intellectual disabilities ; Intellectual disability ; Intelligence ; Intelligenzminderung ; Intelligenzminderung, autosomal-dominant ; Medicine ; Medicine & Public Health ; Mosaicism ; Mosaik ; Mutation ; Next generation sequencing ; Oncology ; Reproductive Medicine ; Schwerpunktthema ; Schwerpunktthema: Intelligenzminderung ; Seizures
    ISSN: 0936-5931
    E-ISSN: 1863-5490
    DOI: 10.1007/s11825-018-0206-2
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/30459487$$D View this record in MEDLINE/PubMed
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  • 2
    Article
    Article
    SARS‐CoV‐2 targets neurons of 3D human brain organoids
    2020
    ISSN: 0261-4189 
    Details
    Language: English
    In: The EMBO journal, 2020-10-15, Vol.39 (20), p.e106230-n/a
    Description: COVID‐19 pandemic caused by SARS‐CoV‐2 infection is a public health emergency. COVID‐19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS‐CoV‐2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS‐CoV‐2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS‐CoV‐2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS‐CoV‐2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS‐CoV‐2 and emphasize that brain organoids could model CNS pathologies of COVID‐19. Synopsis Modelling coronavirus exposure of the central nervous system is critical to assess the cellular tropism and potential neurological consequences of infection. Here, a Düsseldorf isolate of SARS‐CoV‐2 is shown to enter human cerebral organoids and preferably target neuronal cells. Clinical SARS‐CoV-2 strain targets neurons of 3D human brain organoids. SARS‐CoV-2 does not appear to actively proliferate in neurons. SARS‐CoV-2 is associated with Tau abnormalities in neurons. SARS‐CoV-2 induces neuronal cell death. In vitro exposure of cerebral organoids to coronavirus results in preferential infection and cell death of neuronal cells.
    Subject(s): Abnormalities ; Animals ; Axons ; Betacoronavirus - physiology ; Brain ; Brain - virology ; brain organoids ; Cell Death ; Central nervous system ; Chlorocebus aethiops ; Coronaviruses ; COVID-19 ; Exposure ; Humans ; Infections ; Life Sciences ; Microbiology, Virology & Host Pathogen Interaction ; Molecular Biology of Disease ; Nervous system ; Nervous System Diseases - virology ; Neuroimaging ; Neurons ; Neurons - virology ; Neuroscience ; Neurotoxicity ; Organoids ; Pandemics ; Phosphorylation ; Public health ; SARS-CoV-2 ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Tau pathology ; Tau protein ; tau Proteins - metabolism ; Tropism ; Vero Cells ; Viral diseases
    ISSN: 0261-4189
    E-ISSN: 1460-2075
    DOI: 10.15252/embj.2020106230
    Source: HighWire Press (Free Journals)
    Source: PubMed Central
    Source: Get It Now
    URL: https://www.ncbi.nlm.nih.gov/pubmed/32876341$$D View this record in MEDLINE/PubMed
    URL: https://hal.archives-ouvertes.fr/hal-02969415$$DView record in HAL
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  • 3
    Article
    Article
    Mutations in NSUN2 Cause Autosomal- Recessive Intellectual Disability
    2012
    ISSN: 0002-9297 
    Details
    Language: English
    In: American journal of human genetics, 2012-05-04, Vol.90 (5), p.847-855
    Description: With a prevalence between 1 and 3%, hereditary forms of intellectual disability (ID) are among the most important problems in health care. Particularly, autosomal-recessive forms of the disorder have a very heterogeneous molecular basis, and genes with an increased number of disease-causing mutations are not common. Here, we report on three different mutations (two nonsense mutations, c.679C〉T [p.Gln227∗] and c.1114C〉T [p.Gln372∗], as well as one splicing mutation, g.6622224A〉C [p.Ile179Argfs∗192]) that cause a loss of the tRNA-methyltransferase-encoding NSUN2 main transcript in homozygotes. We identified the mutations by sequencing exons and exon-intron boundaries within the genomic region where the linkage intervals of three independent consanguineous families of Iranian and Kurdish origin overlapped with the previously described MRT5 locus. In order to gain further evidence concerning the effect of a loss of NSUN2 on memory and learning, we constructed a Drosophila model by deleting the NSUN2 ortholog, CG6133, and investigated the mutants by using molecular and behavioral approaches. When the Drosophila melanogaster NSUN2 ortholog was deleted, severe short-term-memory (STM) deficits were observed; STM could be rescued by re-expression of the wild-type protein in the nervous system. The humans homozygous for NSUN2 mutations showed an overlapping phenotype consisting of moderate to severe ID and facial dysmorphism (which includes a long face, characteristic eyebrows, a long nose, and a small chin), suggesting that mutations in this gene might even induce a syndromic form of ID. Moreover, our observations from the Drosophila model point toward an evolutionarily conserved role of RNA methylation in normal cognitive development.
    Subject(s): Adolescent ; Adult ; Adult and adolescent clinical studies ; Animals ; Biological and medical sciences ; Child ; Cloning, Molecular ; Codon, Nonsense ; Consanguinity ; DNA sequencing ; Drosophila ; Drosophila - genetics ; Drosophila melanogaster ; Enzymes ; Exons ; Female ; Fundamental and applied biological sciences. Psychology ; Gene mutations ; General aspects. Genetic counseling ; Genes, Recessive ; Genetic aspects ; Genetic Linkage ; Genetic research ; Genetic transcription ; Genetics of eukaryotes. Biological and molecular evolution ; Genotype ; Homozygote ; Humans ; Intellectual deficiency ; Intellectual Disability - genetics ; Intellectual Disability - physiopathology ; Learning disabilities ; Male ; Medical genetics ; Medical sciences ; Memory ; Methylation ; Methyltransferases - genetics ; Methyltransferases - metabolism ; Middle Aged ; Molecular and cellular biology ; Molecular genetics ; Mutation ; Nervous system ; Nucleotide sequencing ; Pedigree ; Phenotype ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Transfer RNA ; Transferases ; Young Adult
    ISSN: 0002-9297
    E-ISSN: 1537-6605
    DOI: 10.1016/j.ajhg.2012.03.021
    Source: Cell Press Collection [ECCPC]
    Source: PubMed Central
    URL: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25863108$$DView record in Pascal Francis
    URL: https://www.ncbi.nlm.nih.gov/pubmed/22541559$$D View this record in MEDLINE/PubMed
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  • 4
    Article
    Article
    Haploinsufficiency of ARID1B, a Member of the SWI/SNF-A Chromatin-Remodeling Complex, Is a Frequent Cause of Intellectual Disability
    2012
    ISSN: 0002-9297 
    Details
    Language: English
    In: American journal of human genetics, 2012-03-09, Vol.90 (3), p.565-572
    Description: Intellectual disability (ID) is a clinically and genetically heterogeneous common condition that remains etiologically unresolved in the majority of cases. Although several hundred diseased genes have been identified in X-linked, autosomal-recessive, or syndromic types of ID, the establishment of an etiological basis remains a difficult task in unspecific, sporadic cases. Just recently, de novo mutations in SYNGAP1, STXBP1, MEF2C, and GRIN2B were reported as relatively common causes of ID in such individuals. On the basis of a patient with severe ID and a 2.5 Mb microdeletion including ARID1B in chromosomal region 6q25, we performed mutational analysis in 887 unselected patients with unexplained ID. In this cohort, we found eight (0.9%) additional de novo nonsense or frameshift mutations predicted to cause haploinsufficiency. Our findings indicate that haploinsufficiency of ARID1B, a member of the SWI/SNF-A chromatin-remodeling complex, is a common cause of ID, and they add to the growing evidence that chromatin-remodeling defects are an important contributor to neurodevelopmental disorders.
    Subject(s): Adolescent ; Adult ; Causes of ; Child ; Child, Preschool ; Chromatin ; Chromatin - genetics ; Chromatin Assembly and Disassembly - genetics ; Chromatin remodeling ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomes ; Cognition disorders ; Cognition in children ; Cohort Studies ; DNA Mutational Analysis - methods ; DNA-Binding Proteins - genetics ; Exons ; Female ; Frameshift mutation ; Gene mutations ; Genetic aspects ; Genetics ; Haploinsufficiency ; Humans ; Intellect ; Intellectual Disability ; Intelligence levels ; Learning disabilities ; Male ; Mental retardation ; Middle Aged ; Mutation ; Neurodevelopmental disorders ; Neurological disorders ; Report ; Transcription Factors - genetics ; X chromosome ; Young Adult
    ISSN: 0002-9297
    E-ISSN: 1537-6605
    DOI: 10.1016/j.ajhg.2012.02.007
    Source: Cell Press Collection [ECCPC]
    Source: PubMed Central
    URL: https://www.ncbi.nlm.nih.gov/pubmed/22405089$$D View this record in MEDLINE/PubMed
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  • 5
    Article
    Article
    Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature
    2018
    ISSN: 1098-3600 
    Details
    Language: English
    In: Genetics in medicine, 2018-06, Vol.20 (6), p.630-638
    Description: PurposeShort stature is a common condition of great concern to patients and their families. Mostly genetic in origin, the underlying cause often remains elusive due to clinical and genetic heterogeneity.MethodsWe systematically phenotyped 565 patients where common nongenetic causes of short stature were excluded, selected 200 representative patients for whole-exome sequencing, and analyzed the identified variants for pathogenicity and the affected genes regarding their functional relevance for growth.ResultsBy standard targeted diagnostic and phenotype assessment, we identified a known disease cause in only 13.6% of the 565 patients. Whole-exome sequencing in 200 patients identified additional mutations in known short-stature genes in 16.5% of these patients who manifested only part of the symptomatology. In 15.5% of the 200 patients our findings were of significant clinical relevance. Heterozygous carriers of recessive skeletal dysplasia alleles represented 3.5% of the cases.ConclusionA combined approach of systematic phenotyping, targeted genetic testing, and whole-exome sequencing allows the identification of the underlying cause of short stature in at least 33% of cases, enabling physicians to improve diagnosis, treatment, and genetic counseling. Exome sequencing significantly increases the diagnostic yield and consequently care in patients with short stature.
    Subject(s): Body Height - genetics ; Female ; Genetic counseling ; Genetic Testing ; growth; phenotypic spectrum ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mutation ; Original ; Pedigree ; Phenotype ; Sequence Analysis, DNA - methods ; short stature; skeletal dysplasia ; Whole Exome Sequencing - methods ; whole-exome sequencing
    ISSN: 1098-3600
    E-ISSN: 1530-0366
    DOI: 10.1038/gim.2017.159
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/29758562$$D View this record in MEDLINE/PubMed
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  • 6
    Article
    Article
    RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA
    2016
    ISSN: 2041-1723 
    Details
    Language: English
    In: Nature communications, 2016-05-27, Vol.7 (1), p.11752-11752
    Description: Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.
    Subject(s): Cells, Cultured ; Cytosol - metabolism ; DNA, Single-Stranded - genetics ; DNA, Single-Stranded - metabolism ; Exodeoxyribonucleases - genetics ; Exodeoxyribonucleases - metabolism ; Fibroblasts - cytology ; Fibroblasts - metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Interferon Type I - metabolism ; Phosphoproteins - genetics ; Phosphoproteins - metabolism ; Protein Binding ; Rad51 Recombinase - genetics ; Rad51 Recombinase - metabolism ; Replication Protein A - genetics ; Replication Protein A - metabolism ; RNA Interference ; Tumor Suppressor Protein p53 - metabolism
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    DOI: 10.1038/ncomms11752
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    URL: https://www.ncbi.nlm.nih.gov/pubmed/27230542$$D View this record in MEDLINE/PubMed
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  • 7
    Article
    Article
    The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis
    2011
    ISSN: 0022-2593 
    Details
    Language: English
    In: Journal of medical genetics, 2011-06, Vol.48 (6), p.396-406
    Description: BackgroundSubmicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients.MethodThe study mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridisation and analysed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array comparative genomic hybridisation. The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals.ResultsOne known mutation, seen in two patients, and nine novel mutations of FOXG1 including two deletions, two chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and seven sequence changes, are reported. Analysis of 11 patients in this study, and a further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastro-oesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria.ConclusionsThese findings have significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the FOXG1 syndrome.
    Subject(s): Artificial chromosomes ; Base Sequence ; Biological and medical sciences ; Child ; Child development deviations ; Child, Preschool ; Children & youth ; Chromosome deletion ; Chromosomes, Human, Pair 14 - chemistry ; clinical genetics ; Cloning ; Comparative Genomic Hybridization ; Congenital diseases ; Corpus Callosum - pathology ; Deoxyribonucleic acid ; Developmental disabilities ; DNA ; Dyskinesias - genetics ; Female ; Forkhead Transcription Factors - genetics ; FOXG1 ; Fundamental and applied biological sciences. Psychology ; Gene mutations ; General aspects. Genetic counseling ; Genes ; Genetic aspects ; Genetic Association Studies ; Genetic testing ; Genetics of eukaryotes. Biological and molecular evolution ; Genomes ; Genotype ; Genotype & phenotype ; Health aspects ; Humans ; Intellectual disabilities ; Intellectual Disability - genetics ; Male ; Malformations of the nervous system ; Medical genetics ; Medical imaging ; Medical sciences ; mental retardation ; Methyl-CpG-Binding Protein 2 - genetics ; microcephaly ; Microcephaly - genetics ; Molecular and cellular biology ; Molecular Sequence Data ; Molecular Typing ; Mutation ; Nerve Tissue Proteins - genetics ; Neurology ; Patients ; Phenotype ; Physiological aspects ; Rett syndrome ; Rett Syndrome - classification ; Rett Syndrome - genetics ; Sequence Deletion ; Software
    ISSN: 0022-2593
    E-ISSN: 1468-6244
    DOI: 10.1136/jmg.2010.087528
    Source: Hellenic Academic Libraries Link
    Source: BMJ Journals - NESLi2
    URL: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24232051$$DView record in Pascal Francis
    URL: https://www.ncbi.nlm.nih.gov/pubmed/21441262$$D View this record in MEDLINE/PubMed
    URL: https://hal.archives-ouvertes.fr/hal-00616882$$DView record in HAL
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  • 8
    Article
    Article
    Family-based germline sequencing in children with cancer
    2019
    ISSN: 0950-9232 
    Details
    Language: English
    In: Oncogene, 2019-02-28, Vol.38 (9), p.1367-1380
    Description: The discovery of cancer-predisposing syndromes (CPSs) using next-generation sequencing (NGS) technologies is of increasing importance in pediatric oncology with regard to diagnosis, treatment, surveillance, family counselling and research. Recent studies indicate that a considerable percentage of childhood cancers are associated with CPSs. However, the ratio of CPSs that are caused by inherited vs. de novo mutations (DNMs), the risk of recurrence, and even the total number of genes, which should be considered as a true cancer-predisposing gene, are still unknown. In contrast to sequencing only single index patients, family-based NGS of the germline is a very powerful tool for providing unique insights into inheritance patterns (e.g., DNMs, parental mosaicism) and types of aberrations (e.g., SNV, CNV, indels, SV). Furthermore, functional perturbations of key cancer pathways (e.g., TP53, FA/BRCA) by at least two co-inherited heterozygous digenic mutations from each parent and currently unrecognized rare variants and unmeasured genetic interactions between common and rare variants may be a widespread genetic phenomenon in the germline of affected children. Therefore, family-based trio sequencing has the potential to reveal a striking new landscape of inheritance in childhood cancer and to facilitate the integration and efforts of individualized treatment strategies, including personalized and preventive medicine and cancer surveillance programs. Consequently, cancer genetics is becoming an increasingly common approach in modern oncology, so trio-sequencing should also be routinely integrated into pediatric oncology.
    Subject(s): Biochemistry & Molecular Biology ; Breast cancer ; Cancer ; Cell Biology ; Children ; Genetics & Heredity ; Heredity ; Life Sciences & Biomedicine ; Medical genetics ; Mosaicism ; Mutation ; Next-generation sequencing ; Oncology ; p53 Protein ; Paediatric cancer ; Pediatrics ; Review ; Science & Technology ; Surveillance
    ISSN: 0950-9232
    E-ISSN: 1476-5594
    DOI: 10.1038/s41388-018-0520-9
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Nature Journals Online
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/30305723$$D View this record in MEDLINE/PubMed
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  • 9
    Article
    Article
    Mutations in U4atac snRNA, a Component of the Minor Spliceosome, in the Developmental Disorder MOPD I
    2011
    ISSN: 0036-8075 
    Details
    Language: English
    In: Science (American Association for the Advancement of Science), 2011-04-08, Vol.332 (6026), p.238-240
    Description: Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G〉A, 51G〉A, 55G〉A, and 111G〉A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.
    Subject(s): Biological and medical sciences ; Cell Line ; Cell lines ; Chromosomes, Human, Pair 2 - genetics ; Classical genetics, quantitative genetics, hybrids ; Developmental disabilities ; Dwarfism - genetics ; Dwarfism - metabolism ; Female ; Fetal Growth Retardation - genetics ; Fetal Growth Retardation - metabolism ; Fibroblasts ; Fundamental and applied biological sciences. Psychology ; Gene mutations ; Genes ; Genetic mutation ; Genetics of eukaryotes. Biological and molecular evolution ; Human ; Humans ; Introns ; Inverted Repeat Sequences ; Male ; Mental disorders ; microcephalic osteodysplastic primordial dwarfism type I ; Microcephaly - genetics ; Microcephaly - metabolism ; minor spliceosome ; Mutation ; Nucleic Acid Conformation ; Nucleic acids ; Observations ; Osteochondrodysplasias - genetics ; Osteochondrodysplasias - metabolism ; Pedigree ; Properties ; REPORTS ; Ribonucleic acid ; RNA ; RNA Splicing ; RNA, Small Nuclear - chemistry ; RNA, Small Nuclear - genetics ; RNA, Small Nuclear - metabolism ; RNU4ATAC ; Sequencing ; Small nuclear RNA ; snRNA ; Spliceosomes ; Spliceosomes - genetics ; Spliceosomes - metabolism ; Splicing
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    DOI: 10.1126/science.1200587
    Source: JSTOR Life Sciences
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: Get It Now
    URL: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24103455$$DView record in Pascal Francis
    URL: https://www.ncbi.nlm.nih.gov/pubmed/21474760$$D View this record in MEDLINE/PubMed
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  • 10
    Article
    Article
    Deep sequencing reveals 50 novel genes for recessive cognitive disorders
    2011
    ISSN: 0028-0836 
    Details
    Language: English
    In: Nature (London), 2011, Vol.478 (7367), p.57-63
    Description: Common diseases are often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. This has been amply documented for early-onset cognitive impairment, or intellectual disability, one of the most complex disorders known and a very important health care problem worldwide. More than 90 different gene defects have been identified for X-chromosome-linked intellectual disability alone, but research into the more frequent autosomal forms of intellectual disability is still in its infancy. To expedite the molecular elucidation of autosomal-recessive intellectual disability, we have now performed homozygosity mapping, exon enrichment and next-generation sequencing in 136 consanguineous families with autosomal-recessive intellectual disability from Iran and elsewhere. This study, the largest published so far, has revealed additional mutations in 23 genes previously implicated in intellectual disability or related neurological disorders, as well as single, probably disease-causing variants in 50 novel candidate genes. Proteins encoded by several of these genes interact directly with products of known intellectual disability genes, and many are involved in fundamental cellular processes such as transcription and translation, cell-cycle control, energy metabolism and fatty-acid synthesis, which seem to be pivotal for normal brain development and function.
    Subject(s): Adult and adolescent clinical studies ; Biological and medical sciences ; Brain - metabolism ; Brain - physiology ; Cell Cycle ; Chromosome mapping ; Cognition disorders ; Cognition Disorders - genetics ; Consanguinity ; Demographic aspects ; DNA Mutational Analysis ; Exons - genetics ; Fundamental and applied biological sciences. Psychology ; Gene Regulatory Networks ; Genes, Essential - genetics ; Genes, Recessive - genetics ; Genetic aspects ; Genetic variation ; Genetics of eukaryotes. Biological and molecular evolution ; High-Throughput Nucleotide Sequencing ; Homozygote ; Human ; Humans ; Intellectual deficiency ; Intellectual Disability - genetics ; Medical sciences ; Metabolic Networks and Pathways ; Mutation - genetics ; Nucleotide sequencing ; Organ Specificity ; Population genetics, reproduction patterns ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Risk factors ; Synapses - metabolism ; Usage
    ISSN: 0028-0836
    E-ISSN: 1476-4687
    DOI: 10.1038/nature10423
    Source: Academic Search Ultimate
    Source: Get It Now
    URL: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24569703$$DView record in Pascal Francis
    URL: https://www.ncbi.nlm.nih.gov/pubmed/21937992$$D View this record in MEDLINE/PubMed
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