Critical region within 22q11.2 linked to higher rate of autism spectrum disorder.

TitleCritical region within 22q11.2 linked to higher rate of autism spectrum disorder.
Publication TypeJournal Article
Year of Publication2017
AuthorsClements, CC, Wenger, TL, Zoltowski, AR, Bertollo, JR, Miller, JS, de Marchena, AB, Mitteer, LM, Carey, JC, Yerys, BE, Zackai, EH, Emanuel, BS, McDonald-McGinn, DM, Schultz, RT
JournalMol Autism
Date Published2017
KeywordsActivities of Daily Living, Adolescent, Adult, Autism Spectrum Disorder, Catechol O-Methyltransferase, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 22, Cohort Studies, Female, Gene Duplication, Humans, Infant, Infant, Newborn, Male, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Psychometrics, Risk, Social Communication Disorder, Young Adult

BACKGROUND: Previous studies have reported no clear critical region for medical comorbidities in children with deletions or duplications of 22q11.2. The purpose of this study was to evaluate whether individuals with small nested deletions or duplications of the LCR-A to B region of 22q11.2 show an elevated rate of autism spectrum disorder (ASD) compared to individuals with deletions or duplications that do not include this region.METHODS: We recruited 46 patients with nested deletions ( = 33) or duplications ( = 13) of 22q11.2, including LCR-A to B ( = 11), LCR-A to C ( = 4), LCR-B to D ( = 14;  = 8), LCR-C to D ( = 4;  = 2), and smaller nested regions ( = 3). Parent questionnaire, record review, and, for a subset, in-person evaluation were used for ASD diagnostic classification. Rates of ASD in individuals with involvement of LCR-B to LCR-D were compared with Fisher's exact test to LCR-A to LCR-B for deletions, and to a previously published sample of LCR-A to LCR-D for duplications. The rates of medical comorbidities and psychiatric diagnoses were determined from questionnaires and chart review. We also report group mean differences on psychiatric questionnaires.RESULTS: Individuals with deletions involving LCR-A to B showed a 39-44% rate of ASD compared to 0% in individuals whose deletions did not involve LCR-A to B. We observed similar rates of medical comorbidities in individuals with involvement of LCR-A to B and LCR-B to D for both duplications and deletions, consistent with prior studies.CONCLUSIONS: Children with nested deletions of 22q11.2 may be at greater risk for autism spectrum disorder if the region includes LCR-A to LCR-B. Replication is needed.

Alternate JournalMol Autism
PubMed ID29090080
PubMed Central IDPMC5658953
Grant ListR01 HD055741 / HD / NICHD NIH HHS / United States
R01 MH107431 / MH / NIMH NIH HHS / United States
U54 HD086984 / HD / NICHD NIH HHS / United States