ABSTRACT
We present clinical data on 33 subjects with additional copies of the Prader-Willi-Angelman critical region (PWACR) contained in a supernumerary marker chromosome (SMC). Twenty-three subjects had a typical large non-mosaic SMC(15) containing two copies of the PWACR. They showed a variable but generally severe phenotype of learning disability and autism, with seizures in approximately two-thirds. The other 10 differed from this typical pattern in respect of mosaicism, variation in copy number, or arrangement of the PWACR within the SMC or number of SMC per cell. Clinical severity increased with the number of additional copies of the PWACR and decreased with mosaicism for a normal cell line. There was a trend for a larger number of seizures to be associated with more severe learning disability. Three subjects with interstitial triplications of 15q11-q13 showed a range of phenotypes similar to those of the typical large SMC(15). All additional copies of the PWACR in this series were maternally-derived. FISH and molecular data localizing the breakpoints of the rearrangements have been previously published or are included in this report. No correlations were found between specific clinical features and variations in breakpoints proximal and distal to the PWACR.
Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 15/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , In Situ Hybridization, Fluorescence , Learning Disabilities/pathology , Male , Middle Aged , MosaicismABSTRACT
This study investigated the phenotypic manifestations of interstitial duplications of chromosome 15 that involve the Prader-Willi/Angelman syndrome critical region (PWACR). Twenty-one affected individuals from six families were evaluated in detail, using standardized and semi-standardized measures of intelligence, psychopathology, and physical anomalies. Special attention was placed on determining the prevalence of autism spectrum disorders as well as the relationship between the parental origin of the duplication and the phenotypic effects. Assessments of the affected individuals were compared with evaluations of the unaffected relatives from the same families. Results indicated that duplications in the region were associated with variable degrees of intellectual impairments and motor coordination problems. Four of the subjects received a diagnosis of pervasive developmental disorder. Three of these cases were probands and only one met criteria for classic autism. There was very little evidence of the duplication cosegregating with autism spectrum disorder diagnosis. Paternally inherited duplications were significantly less likely to give rise to phenotypic effects. The findings indicate that duplications in the PWACR give rise to developmental delay but not necessarily autism spectrum disorders. They also suggest that phenotypic expression is dependent on the parental origin of the duplication and implicate maternally active genes in the pathogenesis of the developmental impairments. Further research will be required to clarify the range and basis of the phenotypic manifestations.
Subject(s)
Autistic Disorder/genetics , Chromosome Aberrations , Chromosomes, Human, Pair 15/genetics , Adult , Autistic Disorder/physiopathology , Autistic Disorder/psychology , Behavior/physiology , Child , Child Development Disorders, Pervasive/physiopathology , Child Development Disorders, Pervasive/psychology , Child, Preschool , Cognition/physiology , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Family Health , Female , Gene Duplication , Heterozygote , Humans , Intelligence Tests , Male , Pedigree , Phenotype , Psychomotor Performance/physiology , Twins, Monozygotic/geneticsABSTRACT
OBJECTIVE: This study aimed to replicate Manning's (1987) research that looked at "Favorite Kind of Day" drawings produced by children who had been maltreated in comparison to non-maltreated children. The hypothesis of the study was that the maltreated children's drawings would consistently differ from drawings produced by non-maltreated children over time. METHOD: Eighteen children aged between 4 and 8 years old were individually asked to draw their "Favorite Kind of Day" (FKD). The drawings from six physically maltreated participants were compared to 12 non-maltreated children matched for age, sex, socio-economic and educational background. The drawings were compared on three criteria: inclement weather, size, and movement of weather. RESULTS: The results showed that over a period of 18 months, maltreated and non-maltreated children consistently drew similar drawings, and no significant differences were found between the groups. CONCLUSIONS: The implications of these findings cannot be underestimated, as clinical use of the FKD technique suggested by Manning's findings, for English children at least, would lead to incorrect identification of children as having suffered maltreatment when they may in fact not have.
