Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA.
J Neurodev Disord. 2010 Sep;2(3):144-8. doi: 10.1007/s11689-010-9051-6. Epub 2010 May 21.
Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the maternal chromosome 15, or uniparental maternal disomy (UPD; the remaining subjects have imprinting center defects. There are several documented physical and behavioral differences between the two major PWS genetic subtypes (deletion and UPD) indicating the genetic subtype plays a role in clinical presentation. Serotonin is known to be disturbed in PWS and affects both eating behavior and compulsion, which are reported to be abnormal in PWS. We investigated the tryptophan hydroxylase gene (TPH2), the rate-limiting enzyme in the production of brain serotonin, by analyzing three different TPH2 gene polymorphisms, transcript expression, and correlation with PWS genetic subtype. DNA and RNA from lymphoblastoid cell lines derived from 12 PWS and 12 comparison subjects were used for the determination of genetic subtype, TPH2 polymorphisms and quantitative RT-PCR analysis. A similar frequency of TPH2 polymorphisms was seen in the PWS and comparison subjects with PWS deletion subjects showing increased expression with one or more TPH2 polymorphism. Both PWS deletion and PWS UPD subjects had significantly lower TPH2 expression than control subjects and PWS deletion subjects had significantly lower TPH2 expression compared with PWS UPD subjects. PWS subjects with 15q11-q13 deletions had lower TPH2 expression compared with PWS UPD or control subjects, requiring replication and further studies to identify the cause including identification of disturbed gene interactions resulting from the deletion process.
普拉德-威利综合征（PWS）是一种遗传性印记疾病，由于来自父染色体 15q11-q13 区域的基因表达缺失，导致发育和行为障碍。在大约 70%的患者中，父染色体的这一部分缺失，而 25%的患者有两条母染色体 15，或单亲二体性母源（UPD；其余患者有印记中心缺陷。两种主要的 PWS 遗传亚型（缺失和 UPD）之间存在几种已记录的身体和行为差异，表明遗传亚型在临床表现中起作用。已知血清素在 PWS 中受到干扰，并且影响进食行为和强迫行为，这些在 PWS 中被报道为异常。我们通过分析三种不同的 TPH2 基因多态性、转录表达以及与 PWS 遗传亚型的相关性，研究了色氨酸羟化酶基因（TPH2），即大脑血清素产生的限速酶。从源自 12 名 PWS 和 12 名对照受试者的淋巴母细胞系中提取 DNA 和 RNA，用于确定遗传亚型、TPH2 多态性和定量 RT-PCR 分析。在 PWS 和对照受试者中，TPH2 多态性的频率相似，PWS 缺失受试者的表达增加，有一个或多个 TPH2 多态性。PWS 缺失和 PWS UPD 受试者的 TPH2 表达均明显低于对照受试者，而 PWS 缺失受试者的 TPH2 表达明显低于 PWS UPD 受试者。与 PWS UPD 或对照受试者相比，携带 15q11-q13 缺失的 PWS 受试者的 TPH2 表达较低，需要进行复制和进一步研究以确定原因，包括确定由于缺失过程而导致的基因相互作用紊乱。
