Mimmack et al. (2002) screened a custom-made cDNA array comprising 300 candidate schizophrenia genes using probes derived from prefrontal cortex tissue of 10 schizophrenia and 10 control brains. The screen revealed a 2.6-fold upregulation of apolipoprotein L1 (APOL1; ... Mimmack et al. (2002) screened a custom-made cDNA array comprising 300 candidate schizophrenia genes using probes derived from prefrontal cortex tissue of 10 schizophrenia and 10 control brains. The screen revealed a 2.6-fold upregulation of apolipoprotein L1 (APOL1; 603743), and this finding was confirmed in prefrontal cortex tissue from the brain collection of the Stanley Foundation and in 20 schizophrenia and 20 control brains from Japan and New Zealand. Mimmack et al. (2002) also found that APOL2 (607252) and APOL4 (607254) were significantly upregulated in schizophrenia. The APOL proteins belong to a group of high density lipoproteins, and all 6 APOL genes are located in close proximity to each other on chromosome 22q12 within the SCZD4 region and close to the region associated with velocardiofacial syndrome, which includes symptoms of schizophrenia. The high density lipoprotein family plays a central role in cholesterol transport. The cholesterol content of membranes is important in cellular processes such as modulating gene transcription and signal transduction both in the adult brain and during neurodevelopment. In 2 sibs with schizophrenia-4 and type I hyperprolinemia, Jacquet et al. (2002) identified a heterozygous deletion of the entire PRODH gene (606810.0001). Two heterozygous mutations in the PRODH gene, leu441 to pro (L441P; 606810.0004) and leu289 to met (L289M; 606810.0003), were identified in 3 of 63 patients with schizophrenia, but not in 68 controls, and were associated with increased plasma proline levels. In the families harboring either the PRODH deletion or the L441P mutation, a second PRODH nucleotide variation cosegregated with higher plasma levels of proline. The authors concluded that type I hyperprolinemia is present in a subset of patients with schizophrenia. Jacquet et al. (2006) reported a lack of association between hyperprolinemia and childhood-onset schizophrenia in a study of 63 subjects and 62 healthy controls matched for age and sex. Xu et al. (2012) sequenced a total of 795 exomes from 231 parent-proband trios enriched for sporadic schizophrenia cases, as well as 34 unaffected trios, and observed in cases an excess of de novo nonsynonymous single-nucleotide polymorphisms (SNPs) as well as a higher prevalence of gene-disruptive de novo mutations relative to controls. Two genes within the 22q11.2 schizophrenia susceptibility locus, DGCR2 (600594) and TOP3B (603582), were altered by both a de novo SNP and a de novo copy number variation (deletion in both cases) in an Afrikaner cohort, one of 2 populations studied.