Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism / Kit San YEUNG in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 66p. Titre : Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism Type de document : texte imprimé Auteurs : Kit San YEUNG, Auteur ; Winnie Wan Yee TSO, Auteur ; Janice Jing Kun IP, Auteur ; Christopher Chun Yu MAK, Auteur ; Gordon Ka Chun LEUNG, Auteur ; Mandy Ho Yin TSANG, Auteur ; Dingge YING, Auteur ; Steven Lim Cho PEI, Auteur ; So Lun LEE, Auteur ; Weipeng YANG, Auteur ; Brian Hon-Yin CHUNG, Auteur Article en page(s) : 66p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Developmental delay  Mtor  Macrocephaly  Megalencephaly  Pik3ca  Ppp2r5d  Pten  Somatic mosaicism  Hong Kong/Hospital Authority Hong Kong West Cluster (UW 12-211), and written  consent was obtained from the patients' parents.Written informed consent was  obtained from the patients' parents for publication of their children's details  and accompanying images in this manuscript. The consent form is held by the  authors and is available for review by the Editor-in-Chief.The authors declare  that they have no competing interests.Springer Nature remains neutral with regard  to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Macrocephaly, which is defined as a head circumference greater than or equal to + 2 standard deviations, is a feature commonly observed in children with developmental delay and/or autism spectrum disorder. Although PTEN is a well-known gene identified in patients with this syndromic presentation, other genes in the PI3K-AKT-mTOR signalling pathway have also recently been suggested to have important roles. The aim of this study is to characterise the mutation spectrum of this group of patients. Methods: We performed whole-exome sequencing of 21 patients with macrocephaly and developmental delay/autism spectrum disorder. Sources of genomic DNA included blood, buccal mucosa and saliva. Germline mutations were validated by Sanger sequencing, whereas somatic mutations were validated by droplet digital PCR. Results: We identified ten pathogenic/likely pathogenic mutations in PTEN (n = 4), PIK3CA (n = 3), MTOR (n = 1) and PPP2R5D (n = 2) in ten patients. An additional PTEN mutation, which was classified as variant of unknown significance, was identified in a patient with a pathogenic PTEN mutation, making him harbour bi-allelic germline PTEN mutations. Two patients harboured somatic PIK3CA mutations, and the level of somatic mosaicism in blood DNA was low. Patients who tested positive for mutations in the PI3K-AKT-mTOR pathway had a lower developmental quotient than the rest of the cohort (DQ = 62.8 vs. 76.1, p = 0.021). Their dysmorphic features were non-specific, except for macrocephaly. Among the ten patients with identified mutations, brain magnetic resonance imaging was performed in nine, all of whom showed megalencephaly. Conclusion: We identified mutations in the PI3K-AKT-mTOR signalling pathway in nearly half of our patients with macrocephaly and developmental delay/autism spectrum disorder. These patients have subtle dysmorphic features and mild developmental issues. Clinically, patients with germline mutations are difficult to distinguish from patients with somatic mutations, and therefore, sequencing of buccal or saliva DNA is important to identify somatic mosaicism. Given the high diagnostic yield and the management implications, we suggest implementing comprehensive genetic testing in the PI3K-AKT-mTOR pathway in the clinical evaluation of patients with macrocephaly and developmental delay and/or autism spectrum disorder. En ligne : http://dx.doi.org/10.1186/s13229-017-0182-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331 [article] Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism [texte imprimé] / Kit San YEUNG, Auteur ; Winnie Wan Yee TSO, Auteur ; Janice Jing Kun IP, Auteur ; Christopher Chun Yu MAK, Auteur ; Gordon Ka Chun LEUNG, Auteur ; Mandy Ho Yin TSANG, Auteur ; Dingge YING, Auteur ; Steven Lim Cho PEI, Auteur ; So Lun LEE, Auteur ; Weipeng YANG, Auteur ; Brian Hon-Yin CHUNG, Auteur . - 66p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 66p. Mots-clés : Autism spectrum disorder  Developmental delay  Mtor  Macrocephaly  Megalencephaly  Pik3ca  Ppp2r5d  Pten  Somatic mosaicism  Hong Kong/Hospital Authority Hong Kong West Cluster (UW 12-211), and written  consent was obtained from the patients' parents.Written informed consent was  obtained from the patients' parents for publication of their children's details  and accompanying images in this manuscript. The consent form is held by the  authors and is available for review by the Editor-in-Chief.The authors declare  that they have no competing interests.Springer Nature remains neutral with regard  to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Macrocephaly, which is defined as a head circumference greater than or equal to + 2 standard deviations, is a feature commonly observed in children with developmental delay and/or autism spectrum disorder. Although PTEN is a well-known gene identified in patients with this syndromic presentation, other genes in the PI3K-AKT-mTOR signalling pathway have also recently been suggested to have important roles. The aim of this study is to characterise the mutation spectrum of this group of patients. Methods: We performed whole-exome sequencing of 21 patients with macrocephaly and developmental delay/autism spectrum disorder. Sources of genomic DNA included blood, buccal mucosa and saliva. Germline mutations were validated by Sanger sequencing, whereas somatic mutations were validated by droplet digital PCR. Results: We identified ten pathogenic/likely pathogenic mutations in PTEN (n = 4), PIK3CA (n = 3), MTOR (n = 1) and PPP2R5D (n = 2) in ten patients. An additional PTEN mutation, which was classified as variant of unknown significance, was identified in a patient with a pathogenic PTEN mutation, making him harbour bi-allelic germline PTEN mutations. Two patients harboured somatic PIK3CA mutations, and the level of somatic mosaicism in blood DNA was low. Patients who tested positive for mutations in the PI3K-AKT-mTOR pathway had a lower developmental quotient than the rest of the cohort (DQ = 62.8 vs. 76.1, p = 0.021). Their dysmorphic features were non-specific, except for macrocephaly. Among the ten patients with identified mutations, brain magnetic resonance imaging was performed in nine, all of whom showed megalencephaly. Conclusion: We identified mutations in the PI3K-AKT-mTOR signalling pathway in nearly half of our patients with macrocephaly and developmental delay/autism spectrum disorder. These patients have subtle dysmorphic features and mild developmental issues. Clinically, patients with germline mutations are difficult to distinguish from patients with somatic mutations, and therefore, sequencing of buccal or saliva DNA is important to identify somatic mosaicism. Given the high diagnostic yield and the management implications, we suggest implementing comprehensive genetic testing in the PI3K-AKT-mTOR pathway in the clinical evaluation of patients with macrocephaly and developmental delay and/or autism spectrum disorder. En ligne : http://dx.doi.org/10.1186/s13229-017-0182-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331

Telehealth-delivered parent-based sleep-focused intervention for insomnia in preschool children with autism spectrum disorder: A randomized controlled study / Brian Yee Ting IP in Autism, 28-11 (November 2024)  

Public ISBD [article]  inAutism > 28-11 (November 2024) . - p.2881 - 2896 Titre : Telehealth-delivered parent-based sleep-focused intervention for insomnia in preschool children with autism spectrum disorder: A randomized controlled study Type de document : texte imprimé Auteurs : Brian Yee Ting IP, Auteur ; So Lun LEE, Auteur ; Shirley Xin LI, Auteur Article en page(s) : p.2881 - 2896 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  children  executive functions  insomnia  intervention  sleep  telehealth Index. décimale : PER Périodiques Résumé : Sleep problems are common in children with autism spectrum disorder. Although previous research has shown the positive effects of parent-based sleep intervention, it was mainly focused on face-to-face modality, which might limit accessibility. This study aimed to examine the efficacy of a telehealth-delivered parent-based sleep-focused intervention in treating insomnia in preschool children with autism spectrum disorder. A total of 62 parents/caregivers with a child with autism spectrum disorder and comorbid insomnia (aged 3 - 6 years) were randomized to receive either three weekly group sessions of sleep-focused intervention via Zoom with telephone support (n = 30) or treatment as usual (n = 32). The intervention group had significantly greater improvements in overall sleep problems (Children s Sleep Habit Questionnaire total score; p < 0.05), bedtime resistance (p < 0.05), and sleep-onset delay (p < 0.05) at post-treatment as compared to the treatment as usual group. The intervention group also showed significant improvements in overall behavioral and emotional problems (p < 0.05), especially externalizing problems (p < 0.05) as measured by Strengths and Difficulties Questionnaire, and parental stress level (p < 0.05) as measured by Depression, Anxiety and Stress Scale-21 as compared to the treatment as usual group (partial 2 = 0.081 - 0.101). The findings supported the feasibility and promising effects of a brief parent-based sleep intervention delivered via telehealth. Lay abstract Sleep problems are common in children with autism spectrum disorder. Although the effects of parent-based sleep intervention were shown to be promising, previous research was limited to the face-to-face service model, which might limit accessibility. This study examined a sleep-focused parent training group delivered via telehealth for treating insomnia in preschool children with autism spectrum disorder, which allowed parents to join the intervention remotely. Results showed that children in the intervention group had greater improvements in sleep and insomnia symptoms after treatment, as compared to those who only received care as usual. This sleep-focused treatment also led to improved daytime behaviors, especially externalizing problems such as hyperactivity and conduct problems, in children with autism spectrum disorder. Parents who had attended the training also reported reduced parental stress level after treatment. The findings supported the feasibility and promising effects of a brief parent-based sleep intervention delivered via telehealth for preschooler with autism spectrum disorder. En ligne : https://dx.doi.org/10.1177/13623613241246502 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] Telehealth-delivered parent-based sleep-focused intervention for insomnia in preschool children with autism spectrum disorder: A randomized controlled study [texte imprimé] / Brian Yee Ting IP, Auteur ; So Lun LEE, Auteur ; Shirley Xin LI, Auteur . - p.2881 - 2896. Langues : Anglais (eng) in Autism > 28-11 (November 2024) . - p.2881 - 2896 Mots-clés : autism spectrum disorder  children  executive functions  insomnia  intervention  sleep  telehealth Index. décimale : PER Périodiques Résumé : Sleep problems are common in children with autism spectrum disorder. Although previous research has shown the positive effects of parent-based sleep intervention, it was mainly focused on face-to-face modality, which might limit accessibility. This study aimed to examine the efficacy of a telehealth-delivered parent-based sleep-focused intervention in treating insomnia in preschool children with autism spectrum disorder. A total of 62 parents/caregivers with a child with autism spectrum disorder and comorbid insomnia (aged 3 - 6 years) were randomized to receive either three weekly group sessions of sleep-focused intervention via Zoom with telephone support (n = 30) or treatment as usual (n = 32). The intervention group had significantly greater improvements in overall sleep problems (Children s Sleep Habit Questionnaire total score; p < 0.05), bedtime resistance (p < 0.05), and sleep-onset delay (p < 0.05) at post-treatment as compared to the treatment as usual group. The intervention group also showed significant improvements in overall behavioral and emotional problems (p < 0.05), especially externalizing problems (p < 0.05) as measured by Strengths and Difficulties Questionnaire, and parental stress level (p < 0.05) as measured by Depression, Anxiety and Stress Scale-21 as compared to the treatment as usual group (partial 2 = 0.081 - 0.101). The findings supported the feasibility and promising effects of a brief parent-based sleep intervention delivered via telehealth. Lay abstract Sleep problems are common in children with autism spectrum disorder. Although the effects of parent-based sleep intervention were shown to be promising, previous research was limited to the face-to-face service model, which might limit accessibility. This study examined a sleep-focused parent training group delivered via telehealth for treating insomnia in preschool children with autism spectrum disorder, which allowed parents to join the intervention remotely. Results showed that children in the intervention group had greater improvements in sleep and insomnia symptoms after treatment, as compared to those who only received care as usual. This sleep-focused treatment also led to improved daytime behaviors, especially externalizing problems such as hyperactivity and conduct problems, in children with autism spectrum disorder. Parents who had attended the training also reported reduced parental stress level after treatment. The findings supported the feasibility and promising effects of a brief parent-based sleep intervention delivered via telehealth for preschooler with autism spectrum disorder. En ligne : https://dx.doi.org/10.1177/13623613241246502 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 / Annisa Shui Lam MAK in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 31p. Titre : Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 Type de document : texte imprimé Auteurs : Annisa Shui Lam MAK, Auteur ; Annie Ting Gee CHIU, Auteur ; Gordon Ka Chun LEUNG, Auteur ; Christopher Chun Yu MAK, Auteur ; Yoyo Wing Yiu CHU, Auteur ; Gary Tsz Kin MOK, Auteur ; Wing Fai TANG, Auteur ; Kelvin Yuen Kwong CHAN, Auteur ; Mary Hoi Yin TANG, Auteur ; Elizabeth Tak-Kwong LAU YIM, Auteur ; Kin Wai SO, Auteur ; Victoria Qinchen TAO, Auteur ; Cheuk Wing FUNG, Auteur ; Virginia C.N. WONG, Auteur ; Mohammed UDDIN, Auteur ; So Lun LEE, Auteur ; Christian R. MARSHALL, Auteur ; Stephen SCHERER, Auteur ; Anita Sik Yau KAN, Auteur ; B.H.Y. CHUNG, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Array comparative genomic hybridization (aCGH)  Autism spectrum disorder (ASD)  Chinese  Copy number variations (CNVs)  Dpp10 Index. décimale : PER Périodiques Résumé : BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. En ligne : http://dx.doi.org/10.1186/s13229-017-0136-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 [texte imprimé] / Annisa Shui Lam MAK, Auteur ; Annie Ting Gee CHIU, Auteur ; Gordon Ka Chun LEUNG, Auteur ; Christopher Chun Yu MAK, Auteur ; Yoyo Wing Yiu CHU, Auteur ; Gary Tsz Kin MOK, Auteur ; Wing Fai TANG, Auteur ; Kelvin Yuen Kwong CHAN, Auteur ; Mary Hoi Yin TANG, Auteur ; Elizabeth Tak-Kwong LAU YIM, Auteur ; Kin Wai SO, Auteur ; Victoria Qinchen TAO, Auteur ; Cheuk Wing FUNG, Auteur ; Virginia C.N. WONG, Auteur ; Mohammed UDDIN, Auteur ; So Lun LEE, Auteur ; Christian R. MARSHALL, Auteur ; Stephen SCHERER, Auteur ; Anita Sik Yau KAN, Auteur ; B.H.Y. CHUNG, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 31p. Mots-clés : Array comparative genomic hybridization (aCGH)  Autism spectrum disorder (ASD)  Chinese  Copy number variations (CNVs)  Dpp10 Index. décimale : PER Périodiques Résumé : BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. En ligne : http://dx.doi.org/10.1186/s13229-017-0136-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

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