Laboratory for Molecular Psychiatry RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Br J Psychiatry. 2011 Sep;199(3):245-6. doi: 10.1192/bjp.bp.111.093849.
The 22q11.2 deletion is the most prominent known genetic risk factor for schizophrenia, but its penetrance is at most approximately 50% suggesting that additional risk factors are required for disease progression. We examined a woman with schizophrenia with this deletion for such risk factors. She had high plasma pentosidine levels ('carbonyl stress') and a frameshift mutation in the responsible gene, GLO1. She also had a constant exotropia, so we examined the PHOX2B gene associated with both schizophrenia and strabismus, and detected a 5-alanine deletion. We propose that the combination of these genetic defects may have exceeded the threshold for the manifestation of schizophrenia.
22q11.2 缺失是精神分裂症最显著的已知遗传风险因素，但它的外显率最高约为 50%，这表明疾病进展还需要其他风险因素。我们检查了一位携带这种缺失的精神分裂症女性患者，她的血浆戊糖素水平（“羰基应激”）较高，且在致病基因 GLO1 中有一个移码突变。她还患有恒定性外斜视，因此我们检查了与精神分裂症和斜视都相关的 PHOX2B 基因，发现了一个 5-丙氨酸缺失。我们提出，这些遗传缺陷的组合可能已经超过了精神分裂症表现的阈值。
