| 1 | Eur. J. Paediatr. Neurol. 2011 May 15: 230-3 |
|---|
| PMID | 21145272 |
| Title | Familial partial trisomy 15q11-13 presenting as intractable epilepsy in the child and schizophrenia in the mother. |
| Abstract | Various rearrangements involve the proximal long arm of chromosome 15, including deletions, duplications, translocations, inversions and supernumerary marker chromosome of an inverted duplication. The large marker 15, that contains the Prader-Willi syndrome (PWS)/Angelman syndrome (AS) chromosome region, is usually associated with an abnormal phenotype of moderate to severe mental retardation, seizures, poor motor coordination, early-onset central hypotonia, autism and autistic-like behavior, schizophrenia and mild dysmorphic features. We report a ten year-old girl with normal intelligence prior to the onset of seizures, who developed severe intractable epilepsy at the age of seven years. Family history was significant for a mother with recurrent episodes of acute psychosis. The patient's and mother's karyotype revealed 47,XX+m. Array comparative genomic hybridization (A-CGH) identified a gain of 13 BAC clones from 15q11.2 through 15q13.1, which was then confirmed by FISH to be part of the marker chromosome. This duplicated region contains the SNRPN/UBE3A locus. This case demonstrates that a duplication of 15q11-13 can present differently in the same family either as intractable epilepsy or as a psychiatric illness and that intelligence can be preserved. We suggest that CGH microarray should be performed in cases with intractable epilepsy or schizophrenia, with or without mental retardation. |
| SCZ Keywords | schizophrenia |
| 2 | Cell 2012 Apr 149: 525-37 |
|---|
| PMID | 22521361 |
| Title | Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. |
| Abstract | Balanced chromosomal abnormalities (BCAs) represent a relatively untapped reservoir of single-gene disruptions in neurodevelopmental disorders (NDDs). We sequenced BCAs in patients with autism or related NDDs, revealing disruption of 33 loci in four general categories: (1) genes previously associated with abnormal neurodevelopment (e.g., AUTS2, FOXP1, and CDKL5), (2) single-gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, and SNURF-SNRPN), (3) novel risk loci (e.g., CHD8, KIRREL3, and ZNF507), and (4) genes associated with later-onset psychiatric disorders (e.g., TCF4, ZNF804A, PDE10A, GRIN2B, and ANK3). We also discovered among neurodevelopmental cases a profoundly increased burden of copy-number variants from these 33 loci and a significant enrichment of polygenic risk alleles from genome-wide association studies of autism and schizophrenia. Our findings suggest a polygenic risk model of autism and reveal that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages. |
| SCZ Keywords | schizophrenia |