Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.
Asperger syndrome (AS) and autistic disorder are two subtypes of pervasive developmental disorders (PDD), but there has been considerable debate over whether AS and autistic disorder without mental retardation (IQ ≥ 70), called high-functioning autism (HFA), are distinct conditions or not. The aim of the present paper was to clarify this issue through a comparison of cognitive function and autistic symptom profiles. Based on the DSM-IV and ICD-10 definitions of language acquisition, 36 age-and IQ-balanced subjects with AS (mean age, 12.8 years; mean full-scale IQ, 98.3) were compared with 37 subjects with HFA (mean age, 12.6 years; mean full-scale IQ, 94.6) on the Japanese version of the Wechsler Intelligence Scales and the Childhood Autism Rating ScaleTokyo Version (CARS-TV). Compared with the HFA subjects, the AS subjects scored significantly higher on Verbal IQ, Vocabulary, and Comprehension, but scored significantly lower on Coding. Although the total CARS-TV score did not differ significantly between the two groups, AS subjects scored significantly lower (i.e. less abnormal) on Verbal communication and Non-verbal communication than did the HFA subjects. A history of normal language acquisition in early childhood could predict his/her better verbal ability in mid-childhood or later. Autistic cognitive characteristics shared by both AS and HFA subjects appear to support the validity of the current diagnostic classification of PDD.
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