Alternative titles; symbols
DO: 0070091;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 22q13.33 | {Schizophrenia 15} | 613950 | Autosomal dominant | 3 | SHANK3 | 606230 |
A number sign (#) is used with this entry because of evidence that susceptibility to schizophrenia-15 (SCZD15) is conferred by variation in the SHANK3 gene (606230) on chromosome 22q13. Mutation in this gene is also involved in autism (see 606232).
For a phenotypic description and a discussion of genetic heterogeneity of schizophrenia, see 181500.
Gauthier et al. (2010) identified a family in which a proband and 2 affected brothers had schizophrenia. The proband was of European ancestry and had a diagnosis of schizoaffective disorder at age 19. He suffered from borderline mental retardation, with an IQ of 73, and had no autistic features. His brother was diagnosed with schizophrenia at age 21 and had a history of hyperactivity in childhood and 1 seizure at age 10. He was described as having mild mental retardation, but no definitive IQ was available. The third brother was diagnosed with schizophrenia and atypical chronic psychosis at age 16. He had moderate mental retardation, with an IQ of 36. The 3 brothers had no evidence of dysmorphic features, and no psychiatric illness was known to be present in the extended family except for major depression in the mother. An individual from a second family, a 23-year-old woman of European ancestry, was diagnosed with schizoaffective disorder at age 11 years. She had normal growth and no evidence of dysmorphic features but had speech impairment and poor academic and social performance with an IQ of 73. She had no evidence of autism on formal testing.
In 3 brothers diagnosed with schizophrenia or schizoaffective disorder, Gauthier et al. (2010) identified a heterozygous R1117X mutation in the SHANK3 gene (606230.0002). The parents were unaffected and did not carry the mutation, which appeared to be inherited from the paternal strand through germline mosaicism. In an unrelated woman diagnosed with a schizoaffective disorder, Gauthier et al. (2010) identified a de novo heterozygous R536W mutation in the SHANK3 gene (606230.0003).
Gauthier, J., Champagne, N., Lafreniere, R. G., Xiong, L., Spiegelman, D., Brustein, E., Lapointe, M., Peng, H., Cote, M., Noreau, A., Hamdan, F. F., Addington, A. M., and 18 others. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc. Nat. Acad. Sci. 107: 7863-7868, 2010. [PubMed: 20385823] [Full Text: https://doi.org/10.1073/pnas.0906232107]