Alternative titles; symbols
DO: 0070093;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9p24.2 | {?Schizophrenia susceptibility 18} | 615232 | 3 | SLC1A1 | 133550 |
A number sign (#) is used with this entry because of evidence that susceptibility to schizophrenia-18 (SCZD18) is conferred by variation in the SLC1A1 gene (133550) on chromosome 9p24. One such family has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of schizophrenia, see 181500.
Myles-Worsley et al. (2013) studied a 5-generation Palauan family (kindred 3501) in which 7 members had a psychotic disorder. Some of the patients who had been diagnosed with schizophrenia had prominent mood symptoms, leading to the diagnosis of schizoaffective disorder.
In several members of a Palauan family (kindred 3501) segregating schizophrenia and schizoaffective disorder, Melhem et al. (2011) identified a deletion at chromosome 9p24.2 containing the SLC21A1 glutamate transporter gene. Using quantitative PCR in an expanded sample of 21 family members, Myles-Worsley et al. (2013) confirmed the deletion of part of the SLC1A1 gene in all 7 family members with psychosis, 3 obligate carrier parents, and 1 unaffected sib, and found that 4 marry-in parents were noncarriers. Linkage analysis under an autosomal dominant model generated a lod score of 3.64, confirming cosegregation of the deletion with psychosis.
In affected members of a 5-generation Palauan family (kindred 3501) segregating schizophrenia and schizoaffective disorder with a deletion at 9p24, Myles-Worsley et al. (2013) demonstrated that an 84,298-bp deletion occurs immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence (including histone binding regions, transcription factor binding regions, and a CpG island), extends through exon 1 of the SLC1A1 mRNA, and removes the first 59 amino acids of the SLC1A1 protein (133550.0001), including the first transmembrane sodium/dicarboxylate symporter domain, one of the domains responsible for glutamate transport. The deletion was not observed in any other Palauans studied, including Palauans with psychiatric disease outside of this family.
Melhem, N., Middleton, F., McFadden, K., Klei, L., Faraone, S. V., Vinogradov, S., Tiobech, J., Yano, V., Kuartei, S., Roeder, K., Byerley, W., Devlin, B., Myles-Worsley, M. Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: risk and transmission in extended pedigrees. Biol. Psychiatry 70: 1115-1121, 2011. [PubMed: 21982423] [Full Text: https://doi.org/10.1016/j.biopsych.2011.08.009]
Myles-Worsley, M., Tiobech, J., Browning, S. R., Korn, J., Goodman, S., Gentile, K., Melhem, N., Byerley, W., Faraone, S. V., Middleton, F. A. Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family. Am. J. Med. Genet. 162B: 87-95, 2013. [PubMed: 23341099] [Full Text: https://doi.org/10.1002/ajmg.b.32125]