Lyu Nan, Guan Li-Li, Ma Hong, Wang Xi-Jin, Wu Bao-Ming, Shang Fan-Hong, Wang Dan, Wen Hong, Yu Xin
Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing 100191, China.
Chin Med J (Engl). 2016 Mar 20;129(6):690-5. doi: 10.4103/0366-6999.178009.
Schizophrenia (SCZ) is a severe, debilitating, and complex psychiatric disorder with multiple causative factors. An increasing number of studies have determined that rare variations play an important role in its etiology. A somatic mutation is a rare form of genetic variation that occurs at an early stage of embryonic development and is thought to contribute substantially to the development of SCZ. The aim of the study was to explore the novel pathogenic somatic single nucleotide variations (SNVs) and somatic insertions and deletions (indels) of SCZ.
One Chinese family with a monozygotic (MZ) twin pair discordant for SCZ was included. Whole exome sequencing was performed in the co-twin and their parents. Rigorous filtering processes were conducted to prioritize pathogenic somatic variations, and all identified SNVs and indels were further confirmed by Sanger sequencing.
One somatic SNV and two somatic indels were identified after rigorous selection processes. However, none was validated by Sanger sequencing.
This study is not alone in the failure to identify pathogenic somatic variations in MZ twins, suggesting that exonic somatic variations are extremely rare. Further efforts are warranted to explore the potential genetic mechanism of SCZ.
精神分裂症（SCZ）是一种严重、使人衰弱且复杂的精神疾病，有多种致病因素。越来越多的研究已确定罕见变异在其病因学中起重要作用。体细胞突变是一种罕见的基因变异形式，发生在胚胎发育早期，被认为对精神分裂症的发展有重大影响。本研究的目的是探索精神分裂症新的致病性体细胞单核苷酸变异（SNV）和体细胞插入缺失（indel）。
纳入一个中国家庭，该家庭中有一对同卵（MZ）双胞胎，其中一人患有精神分裂症，另一人未患病。对患病双胞胎及其父母进行全外显子组测序。进行严格的筛选过程以确定致病性体细胞变异的优先级，所有鉴定出的SNV和indel均通过桑格测序进一步确认。
经过严格筛选后，鉴定出一个体细胞SNV和两个体细胞indel。然而，桑格测序均未验证这些变异。
本研究并非唯一未能在同卵双胞胎中鉴定出致病性体细胞变异的研究，这表明外显子体细胞变异极其罕见。有必要进一步努力探索精神分裂症潜在的遗传机制。
