Alternative titles; symbolsSCHIZOPHRENIA SUSCEPTIBILITY LOCUS, CHROMOSOME 15q15-RELATEDCATATONIA, PERIODICCytogenetic location: 15q15 Genomic coordinates (GR...
Alternative titles; symbols
Cytogenetic location: 15q15 Genomic coordinates (GRCh38): 15:43,300,000-44,500,000
▼ Clinical Features
A clinical subtype of schizophrenia, termed periodic catatonia, is characterized by derangements of facial expression and gestures, so-called psychomotor disturbances (Leonhard, 1999). Catatonia can exhibit 2 psychotic poles: psychomotor excitement and inhibition. Features include grimacing or mask-like facies, iterations, and posture stereotypes, distorted stiff movements, or parakinesis, and akinetic negativism. Acute psychotic episodes may be accompanied by hallucinations and delusions, but, in remission, there remains a distinct mild to severe catatonic residual state with psychomotor weakness of facial expression and diminished incentive.
Stober et al. (1995) and Beckmann et al. (1996) predicted a major gene effect in periodic catatonia because of a morbidity risk of 26.9% in first-degree relatives.
In a genomewide linkage study, Stober et al. (2000) found evidence for a major susceptibility locus on chromosome 15q15 in most of the pedigrees analyzed (maximum nonparametric lod score of 3.57), and a further potential locus on 22q13 (see 600850), pointing to genetic heterogeneity in periodic catatonia.
Stober et al. (2002) performed a genome scan in 4 multiplex families with periodic catatonia and confirmed mapping of a major gene locus on 15q15. Analysis of individual families revealed that 1 large family showed linkage, whereas 2 others could be clearly excluded, which confirmed genetic heterogeneity. Haplotype analysis of chromosome 15 in this and previously linked families placed the susceptibility region in an 11-cM interval between markers D15S1042 and D15S659.
Xu et al. (2012) sequenced a total of 795 exomes from 231 parent-proband trios enriched for sporadic schizophrenia cases from Afrikaner and U.S cohorts, as well as 34 unaffected trios, and observed in cases an excess of de novo nonsynonymous single-nucleotide variants as well as a higher prevalence of gene-disruptive de novo mutations relative to controls. Xu et al. (2012) found 4 genes, LAMA2 (156225), DPYD, (612779), TRRAP (603015), and VPS39 (612188), affected by recurrent de novo events within or across the 2 populations, which is unlikely to have occurred by chance. Xu et al. (2012) identified a missense and splice site mutation in VPS39 occurring as a de novo event in 2 individuals with schizophrenia, 1 from a U.S. population and 1 from an Afrikaner population. VPS39 is within the SCZD10 critical interval. Xu et al. (2012) showed that de novo mutations affect genes with diverse functions and developmental profiles, but they also found a substantial contribution of mutations in genes with higher expression in early fetal life.