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Case Report: Whole Exome Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient With Autism Spectrum Disorder, Intellectual Disability, Hyperactivity, Sleep and Gastrointestinal Disturbances.
Cerminara, Maria; Spirito, Giovanni; Pisciotta, Livia; Squillario, Margherita; Servetti, Martina; Divizia, Maria Teresa; Lerone, Margherita; Berloco, Bianca; Boeri, Silvia; Nobili, Lino; Vozzi, Diego; Sanges, Remo; Gustincich, Stefano; Puliti, Aldamaria.
Afiliación
  • Cerminara M; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
  • Spirito G; Neuroscience Area, International School for Advanced Studies (SISSA), Trieste, Italy.
  • Pisciotta L; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
  • Squillario M; Child Neuropsychiatry Unit, Azienda Socio Sanitaria Territoriale Fatebenefratelli Sacco (ASST Fbf Sacco), Milan, Italy.
  • Servetti M; Medical Genetics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Divizia MT; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
  • Lerone M; Medical Genetics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Berloco B; Medical Genetics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Boeri S; Medical Genetics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Nobili L; Child Neuropsychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Vozzi D; Child Neuropsychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Sanges R; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
  • Gustincich S; Child Neuropsychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
  • Puliti A; Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
Front Genet ; 12: 625564, 2021.
Article en En | MEDLINE | ID: mdl-33679889
Autism Spectrum Disorder (ASD) refers to a broad range of conditions characterized by difficulties in communication, social interaction and behavior, and may be accompanied by other medical or psychiatric conditions. Patients with ASD and comorbidities are often difficult to diagnose because of the tendency to consider the multiple symptoms as the presentation of a complicated syndromic form. This view influences variant filtering which might ignore causative variants for specific clinical features shown by the patient. Here we report on a male child diagnosed with ASD, showing cognitive and motor impairments, stereotypies, hyperactivity, sleep, and gastrointestinal disturbances. The analysis of whole exome sequencing (WES) data with bioinformatic tools for oligogenic diseases helped us to identify two major previously unreported pathogenetic variants: a maternally inherited missense variant (p.R4122H) in HUWE1, an ubiquitin protein ligase associated to X-linked intellectual disability and ASD; and a de novo stop variant (p.Q259X) in TPH2, encoding the tryptophan hydroxylase 2 enzyme involved in serotonin synthesis and associated with susceptibility to attention deficit-hyperactivity disorder (ADHD). TPH2, expressed in central and peripheral nervous tissues, modulates various physiological functions, including gut motility and sleep. To the best of our knowledge, this is the first case presenting with ASD, cognitive impairment, sleep, and gastrointestinal disturbances linked to both HUWE1 and TPH2 genes. Our findings could contribute to the existing knowledge on clinical and genetic diagnosis of patients with ASD presentation with comorbidities.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Genet Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Genet Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza