title: A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis.
abstract: Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5-7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk.
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida 33136, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Griswold
authors.forename: Deqiong
authors.initials: D
authors.lastname: Ma
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Sacharow
authors.forename: Joycelyn L
authors.initials: JL
authors.lastname: Robinson
authors.forename: James M
authors.initials: JM
authors.lastname: Jaworski
authors.forename: Harry H
authors.initials: HH
authors.lastname: Wright
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Abramson
authors.forename: Helle
authors.initials: H
authors.lastname: Lybaek
authors.forename: Nina
authors.initials: N
authors.lastname: Øyen
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000293:Adolescent; D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D015897:Comorbidity; D056915:DNA Copy Number Variations / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000235:genetics*
chemical_list: D015778:Minor Histocompatibility Antigens; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)