Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism View Full Text


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Article Info

DATE

2017-12-20

AUTHORS

Kit San Yeung, Winnie Wan Yee Tso, Janice Jing Kun Ip, Christopher Chun Yu Mak, Gordon Ka Chun Leung, Mandy Ho Yin Tsang, Dingge Ying, Steven Lim Cho Pei, So Lun Lee, Wanling Yang, Brian Hon-Yin Chung

ABSTRACT

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. More... »

PAGES

66

References to SciGraph publications

  • 2013-10-28. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency in NATURE IMMUNOLOGY
  • 2013-03-21. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions in GENETICS IN MEDICINE
  • 2009-02. The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly in GENETICS IN MEDICINE
  • 2014-01-31. PI3K and cancer: lessons, challenges and opportunities in NATURE REVIEWS DRUG DISCOVERY
  • 2017-02-16. Early brain development in infants at high risk for autism spectrum disorder in NATURE
  • 2012-06-24. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes in NATURE GENETICS
  • 2007-05. Genetic testing in autism: how much is enough? in GENETICS IN MEDICINE
  • 2017-05-23. Brief Report: Association Between Autism Spectrum Disorder, Gastrointestinal Problems and Perinatal Risk Factors Within Sibling Pairs in JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
  • 2014-04-06. De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in NATURE GENETICS
  • 2015-11-17. De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism in NEUROGENETICS
  • 2015-10-07. A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 1997-08. Germline mutations in PTEN are present in Bannayan-Zonana syndrome in NATURE GENETICS
  • 2014-10-07. Molecular and Phenotypic Abnormalities in Individuals with Germline Heterozygous PTEN Mutations and Autism in MOLECULAR PSYCHIATRY
  • 2006-09. College News in GENETICS IN MEDICINE
  • 2012-06-24. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly in NATURE GENETICS
  • 2017-03-06. Autism genetics: opportunities and challenges for clinical translation in NATURE REVIEWS GENETICS
  • 2017-03-06. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder in NATURE NEUROSCIENCE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13229-017-0182-4

    DOI

    http://dx.doi.org/10.1186/s13229-017-0182-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1099738469

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29296277


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        "description": "Background: Macrocephaly, which is defined as a head circumference greater than or equal to +\u20092 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.\nMethods: 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.\nResults: We identified ten pathogenic/likely pathogenic mutations in PTEN (n\u2009=\u20094), PIK3CA (n\u2009=\u20093), MTOR (n\u2009=\u20091) and PPP2R5D (n\u2009=\u20092) 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\u00a0(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.\nConclusion: 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.", 
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