title: Comprehensive molecular testing in patients with high functioning autism spectrum disorder.
abstract: Autism spectrum disorders (ASD) include a range of complex neurodevelopmental disorders with extreme genetic heterogeneity. Exome and target sequencing studies have shown to be an effective tool for the discovery of new ASD genes. The aim of this study was to design an ASD candidate gene panel that covers 44 of the top ASD candidate genes. As a pilot study we performed comprehensive molecular diagnostic testing, including the study of the FMR1 and FMR2 repeat regions, copy number variant analysis in a collection of 50 Spanish ASD cases and mutation screening using targeted next generation sequencing-based techniques in 44 out of the total cohort. We evaluated and clinically selected our cohort, with most of the cases having high functioning ASD without facial dysmorphic features. The results of the present study allowed the detection of copy number and single nucleotide variants not yet identified. In addition, our results underscore the difficulty of the molecular diagnosis of ASD and confirm its genetic heterogeneity. The information gained from this and other genetic screenings is necessary to unravel the clinical interpretation of novel variants.
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain; CIBER of Rare Diseases (CIBERER), Villarroel 170, 08036 Barcelona, Spain; IDIBAPS, Rosselló 149, 08036 Barcelona, Spain. Electronic address: misabel_alvarez@hotmail.com.
authors: Maria Isabel
authors: MI
authors: Alvarez-Mora
authors: Child and Adolescent Psychiatry Department, Hospital Clinic, SGR-1119, CIBERSAM, Villarroel 170, 08036 Barcelona, Spain. Electronic address: rcalvo@clinic.ub.es.
authors: Rosa
authors: R
authors: Calvo Escalona
authors: Child and Adolescent Psychiatry Department, Hospital Clinic, SGR-1119, CIBERSAM, Villarroel 170, 08036 Barcelona, Spain. Electronic address: opuig@clinic.cat.
authors: Olga
authors: O
authors: Puig Navarro
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain; CIBER of Rare Diseases (CIBERER), Villarroel 170, 08036 Barcelona, Spain; IDIBAPS, Rosselló 149, 08036 Barcelona, Spain. Electronic address: imadbajo@clinic.ub.es.
authors: Irene
authors: I
authors: Madrigal
authors: Genomic Medicine Group-Santiago de Compostela University, CEGEN-PRB2-ISCIII, Travesía da Choupana, s/n, 15706 Santiago de Compostela, A Coruña, Spain. Electronic address: ines.quintela@usc.es.
authors: Ines
authors: I
authors: Quintela
authors: Genomic Medicine Group-Santiago de Compostela University, CEGEN-PRB2-ISCIII, Travesía da Choupana, s/n, 15706 Santiago de Compostela, A Coruña, Spain; Genomic Medicine Group, CIBERER, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Travesía da Choupana, s/n, 15706 Santiago de Compostela, A Coruña, Spain. Electronic address: jorge.amigo@usc.es.
authors: Jorge
authors: J
authors: Amigo
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. Electronic address: deielurbe@gmail.com.
authors: Dei
authors: D
authors: Martinez-Elurbe
authors: Pediatric Service, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain. Electronic address: MLinder@parcdesalutmar.cat.
authors: Michaela
authors: M
authors: Linder-Lucht
authors: Pediatric Service, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain; Autonoma University of Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain. Electronic address: GAznar@parcdesalutmar.cat.
authors: Gemma
authors: G
authors: Aznar Lain
authors: Genomic Medicine Group-Santiago de Compostela University, CEGEN-PRB2-ISCIII, Travesía da Choupana, s/n, 15706 Santiago de Compostela, A Coruña, Spain; Genomic Medicine Group, CIBERER, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Travesía da Choupana, s/n, 15706 Santiago de Compostela, A Coruña, Spain; King Abdulaziz University, Center of Excellence in Genomic Medicine Research, Abdullah Sulayman, Jeddah 22254, Saudi Arabia. Electronic address: angel.carracedo@usc.es.
authors: Angel
authors: A
authors: Carracedo
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain; CIBER of Rare Diseases (CIBERER), Villarroel 170, 08036 Barcelona, Spain; IDIBAPS, Rosselló 149, 08036 Barcelona, Spain. Electronic address: mmila@clinic.ub.es.
authors: Montserrat
authors: M
authors: Mila
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain; CIBER of Rare Diseases (CIBERER), Villarroel 170, 08036 Barcelona, Spain; IDIBAPS, Rosselló 149, 08036 Barcelona, Spain. Electronic address: lbodi@clinic.ub.es.
authors: Laia
authors: L
authors: Rodriguez-Revenga
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D018628:Gene Dosage; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010865:Pilot Projects
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009687:Nuclear Proteins; C099930:AFF2 protein, human; C497683:FMR1 protein, human
keywords: Autism spectrum disorders; Candidate genes; Copy number variants; Next generation sequencing; Single nucleotide variants