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Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder / Ashok PATOWARY in Autism Research, 10-8 (August 2017)
[article]
Titre : Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Ashok PATOWARY, Auteur ; Ryan NESBITT, Auteur ; Marilyn ARCHER, Auteur ; Raphael BERNIER, Auteur ; Zoran BRKANAC, Auteur Article en page(s) : p.1338-1343 Langues : Anglais (eng) Mots-clés : mitochondria autism spectrum disorder whole exome sequencing single nucleotide variation next generation sequencing Index. décimale : PER Périodiques Résumé : Autism is a complex genetic disorder where both de-novo and inherited genetics factors play a role. Next generation sequencing approaches have been extensively used to identify rare variants associated with autism. To date, all such studies were focused on nuclear genome; thereby leaving the role of mitochondrial DNA (mtDNA) variation in autism unexplored. Recently, analytical tools have been developed to evaluate mtDNA in whole-exome data. We have analyzed the mtDNA sequence derived from whole-exome sequencing in 10 multiplex families. In one of the families we have identified two variants of interest in MT-ND5 gene that were previously determined to impair mitochondrial function. In addition in a second family we have identified two VOIs; mtDNA variant in MT-ATP6 and nuclear DNA variant in NDUFS4, where both VOIs are within mitochondrial Respiratory Chain Complex. Our findings provide further support for the role of mitochondria in ASD and confirm that whole-exome sequencing allows for analysis of mtDNA, which sets a stage for further comprehensive genetic investigations of the role of mitochondria in autism. En ligne : http://dx.doi.org/10.1002/aur.1792 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=310
in Autism Research > 10-8 (August 2017) . - p.1338-1343[article] Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Ashok PATOWARY, Auteur ; Ryan NESBITT, Auteur ; Marilyn ARCHER, Auteur ; Raphael BERNIER, Auteur ; Zoran BRKANAC, Auteur . - p.1338-1343.
Langues : Anglais (eng)
in Autism Research > 10-8 (August 2017) . - p.1338-1343
Mots-clés : mitochondria autism spectrum disorder whole exome sequencing single nucleotide variation next generation sequencing Index. décimale : PER Périodiques Résumé : Autism is a complex genetic disorder where both de-novo and inherited genetics factors play a role. Next generation sequencing approaches have been extensively used to identify rare variants associated with autism. To date, all such studies were focused on nuclear genome; thereby leaving the role of mitochondrial DNA (mtDNA) variation in autism unexplored. Recently, analytical tools have been developed to evaluate mtDNA in whole-exome data. We have analyzed the mtDNA sequence derived from whole-exome sequencing in 10 multiplex families. In one of the families we have identified two variants of interest in MT-ND5 gene that were previously determined to impair mitochondrial function. In addition in a second family we have identified two VOIs; mtDNA variant in MT-ATP6 and nuclear DNA variant in NDUFS4, where both VOIs are within mitochondrial Respiratory Chain Complex. Our findings provide further support for the role of mitochondria in ASD and confirm that whole-exome sequencing allows for analysis of mtDNA, which sets a stage for further comprehensive genetic investigations of the role of mitochondria in autism. En ligne : http://dx.doi.org/10.1002/aur.1792 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=310 Brief Report: SETD2 Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy / Heidi S. LUMISH in Journal of Autism and Developmental Disorders, 45-11 (November 2015)
[article]
Titre : Brief Report: SETD2 Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy Type de document : Texte imprimé et/ou numérique Auteurs : Heidi S. LUMISH, Auteur ; Julia WYNN, Auteur ; Orrin DEVINSKY, Auteur ; Wendy K. CHUNG, Auteur Article en page(s) : p.3764-3770 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Autism SETD2 Intellectual disability Whole exome sequencing Index. décimale : PER Périodiques Résumé : Whole exome sequencing (WES) has been utilized with increasing frequency to identify mutations underlying rare diseases. Autism spectrum disorders (ASD) and intellectual disability (ID) are genetically heterogeneous, and novel genes for these disorders are rapidly being identified, making these disorders ideal candidates for WES. Here we report a 17-year-old girl with ASD, developmental delay, ID, seizures, Chiari I malformation, macrocephaly, and short stature. She was found by WES to have a de novo c.2028delT (P677LfsX19) mutation in the SET domain-containing protein 2 (SETD2) gene, predicted to be gene-damaging. This case offers evidence for the potential the role of SETD2 in ASD and ID and provides further detail about the phenotypic manifestations of mutations in SETD2. En ligne : http://dx.doi.org/10.1007/s10803-015-2484-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=270
in Journal of Autism and Developmental Disorders > 45-11 (November 2015) . - p.3764-3770[article] Brief Report: SETD2 Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy [Texte imprimé et/ou numérique] / Heidi S. LUMISH, Auteur ; Julia WYNN, Auteur ; Orrin DEVINSKY, Auteur ; Wendy K. CHUNG, Auteur . - p.3764-3770.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 45-11 (November 2015) . - p.3764-3770
Mots-clés : Autism spectrum disorder Autism SETD2 Intellectual disability Whole exome sequencing Index. décimale : PER Périodiques Résumé : Whole exome sequencing (WES) has been utilized with increasing frequency to identify mutations underlying rare diseases. Autism spectrum disorders (ASD) and intellectual disability (ID) are genetically heterogeneous, and novel genes for these disorders are rapidly being identified, making these disorders ideal candidates for WES. Here we report a 17-year-old girl with ASD, developmental delay, ID, seizures, Chiari I malformation, macrocephaly, and short stature. She was found by WES to have a de novo c.2028delT (P677LfsX19) mutation in the SET domain-containing protein 2 (SETD2) gene, predicted to be gene-damaging. This case offers evidence for the potential the role of SETD2 in ASD and ID and provides further detail about the phenotypic manifestations of mutations in SETD2. En ligne : http://dx.doi.org/10.1007/s10803-015-2484-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=270 Three Brothers With Autism Carry a Stop-Gain Mutation in the HPA-Axis Gene NR3C2 / Holly N. CUKIER in Autism Research, 13-4 (April 2020)
[article]
Titre : Three Brothers With Autism Carry a Stop-Gain Mutation in the HPA-Axis Gene NR3C2 Type de document : Texte imprimé et/ou numérique Auteurs : Holly N. CUKIER, Auteur ; Anthony J. GRISWOLD, Auteur ; Natalia K. HOFMANN, Auteur ; Lissette GOMEZ, Auteur ; Patrice L. WHITEHEAD, Auteur ; Ruth K. ABRAMSON, Auteur ; John R. GILBERT, Auteur ; Michael L. CUCCARO, Auteur ; Derek M. DYKXHOORN, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Article en page(s) : p.523-531 Langues : Anglais (eng) Mots-clés : nuclear receptor subfamily 3 group C member 2 (NR3C2) hypothalamic-pituitary-adrenal (HPA) axis mineralocorticoid receptor (MR) whole exome sequencing Index. décimale : PER Périodiques Résumé : Whole exome sequencing and copy-number variant analysis was performed on a family with three brothers diagnosed with autism. Each of the siblings shares an alteration in the nuclear receptor subfamily 3 group C member 2 (NR3C2) gene that is predicted to result in a stop-gain mutation (p.Q919X) in the mineralocorticoid receptor (MR) protein. This variant was maternally inherited and provides further evidence for a connection between the NR3C2 and autism. Interestingly, the NR3C2 gene encodes the MR protein, a steroid hormone-regulated transcription factor that acts in the hypothalamic-pituitary-adrenal axis and has been connected to stress and anxiety, both of which are features often seen in individuals with autism. Autism Res 2020, 13: 523-531. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Given the complexity of the genetics underlying autism, each gene contributes to risk in a relatively small number of individuals, typically less than 1% of all autism cases. Whole exome sequencing of three brothers with autism identified a rare variant in the nuclear receptor subfamily 3 group C member 2 gene that is predicted to strongly interfere with its normal function. This gene encodes the mineralocorticoid receptor protein, which plays a role in how the body responds to stress and anxiety, features that are often elevated in people diagnosed with autism. This study adds further support to the relevance of this gene as a risk factor for autism. En ligne : http://dx.doi.org/10.1002/aur.2269 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421
in Autism Research > 13-4 (April 2020) . - p.523-531[article] Three Brothers With Autism Carry a Stop-Gain Mutation in the HPA-Axis Gene NR3C2 [Texte imprimé et/ou numérique] / Holly N. CUKIER, Auteur ; Anthony J. GRISWOLD, Auteur ; Natalia K. HOFMANN, Auteur ; Lissette GOMEZ, Auteur ; Patrice L. WHITEHEAD, Auteur ; Ruth K. ABRAMSON, Auteur ; John R. GILBERT, Auteur ; Michael L. CUCCARO, Auteur ; Derek M. DYKXHOORN, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - p.523-531.
Langues : Anglais (eng)
in Autism Research > 13-4 (April 2020) . - p.523-531
Mots-clés : nuclear receptor subfamily 3 group C member 2 (NR3C2) hypothalamic-pituitary-adrenal (HPA) axis mineralocorticoid receptor (MR) whole exome sequencing Index. décimale : PER Périodiques Résumé : Whole exome sequencing and copy-number variant analysis was performed on a family with three brothers diagnosed with autism. Each of the siblings shares an alteration in the nuclear receptor subfamily 3 group C member 2 (NR3C2) gene that is predicted to result in a stop-gain mutation (p.Q919X) in the mineralocorticoid receptor (MR) protein. This variant was maternally inherited and provides further evidence for a connection between the NR3C2 and autism. Interestingly, the NR3C2 gene encodes the MR protein, a steroid hormone-regulated transcription factor that acts in the hypothalamic-pituitary-adrenal axis and has been connected to stress and anxiety, both of which are features often seen in individuals with autism. Autism Res 2020, 13: 523-531. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Given the complexity of the genetics underlying autism, each gene contributes to risk in a relatively small number of individuals, typically less than 1% of all autism cases. Whole exome sequencing of three brothers with autism identified a rare variant in the nuclear receptor subfamily 3 group C member 2 gene that is predicted to strongly interfere with its normal function. This gene encodes the mineralocorticoid receptor protein, which plays a role in how the body responds to stress and anxiety, features that are often elevated in people diagnosed with autism. This study adds further support to the relevance of this gene as a risk factor for autism. En ligne : http://dx.doi.org/10.1002/aur.2269 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder / B. MAHJANI in Molecular Autism, 12 (2021)
[article]
Titre : Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : B. MAHJANI, Auteur ; S. DE RUBEIS, Auteur ; C. GUSTAVSSON MAHJANI, Auteur ; M. MULHERN, Auteur ; X. XU, Auteur ; L. KLEI, Auteur ; F. K. SATTERSTROM, Auteur ; J. FU, Auteur ; Michael E. TALKOWSKI, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; D. E. GRICE, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : 65 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Copy number variant Intellectual disability Pages Single nucleotide variant Whole exome sequencing that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV). METHODS: SNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes. RESULTS: Of 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy. LIMITATIONS: The cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification. CONCLUSIONS: In this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00465-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 65 p.[article] Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder [Texte imprimé et/ou numérique] / B. MAHJANI, Auteur ; S. DE RUBEIS, Auteur ; C. GUSTAVSSON MAHJANI, Auteur ; M. MULHERN, Auteur ; X. XU, Auteur ; L. KLEI, Auteur ; F. K. SATTERSTROM, Auteur ; J. FU, Auteur ; Michael E. TALKOWSKI, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; D. E. GRICE, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur ; Joseph D. BUXBAUM, Auteur . - 65 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 65 p.
Mots-clés : Autism spectrum disorder Copy number variant Intellectual disability Pages Single nucleotide variant Whole exome sequencing that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV). METHODS: SNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes. RESULTS: Of 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy. LIMITATIONS: The cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification. CONCLUSIONS: In this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00465-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459