Whittington J, Holland A, Webb T, Butler J, Clarke D, Boer H
Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, Cambridge, UK.
J Intellect Disabil Res. 2004 Feb;48(Pt 2):172-87. doi: 10.1111/j.1365-2788.2004.00556.x.
Prader-Willi syndrome (PWS) is characterized by extreme floppiness at birth, impaired sexual development, short stature, severe over-eating, characteristic physical features and learning disabilities (LD). Impaired social cognition, literal mindedness and cognitive inflexibility are also present. The syndrome has two main genetic subtypes that both result in the failure of expression of maternally imprinted genes on chromosome 15 at the locus q11-13.
Through multiple sources, we attempted to identify all people with PWS living in one health region in the UK. Additional people with PWS identified in other regions were also recruited to augment the study sample. A comparison group of people with LD as a result of aetiologies other than PWS was also identified. All people from these three groups, over age three, who gave their consent, were assessed using tests of ability and attainment. In addition, their main carers were interviewed using a semistructured interview. Blood samples for genetic diagnosis were obtained from all consenting participants.
The IQ distribution of the population sample was approximately normal with a mean IQ 40 points below that of the general population. There were systematic differences between the two main genetic subtypes. Those with disomies differed in cognitive profiles from both those with deletions and the comparison LD group (the latter two groups were very similar) in terms of better verbal abilities and impaired coding ability. Some people with PWS deletions had strong visuospatial skills.
We propose that the normal distribution of IQ, shifted downwards relative to that of the general population, is the result of a global effect on IQ of the PWS gene(s), and that the different cognitive profile seen in those with chromosome 15 maternal disomies is a specific effect of a gene, or genes, on chromosome 15 which is differentially either expressed or not expressed in those with disomies relative to those with deletions. One hypothesis is that these subtle cognitive differences are a manifestation of the genetic influences of gender-specific imprinted genes on cerebral lateralization. This requires further investigation.
普拉德-威利综合征（PWS）的特征是出生时极度松弛、性发育受损、身材矮小、严重暴饮暴食、具有特征性的身体特征和学习障碍（LD）。还存在社会认知受损、思维刻板和认知灵活性不足的情况。该综合征有两种主要的遗传亚型，均导致位于染色体15q11 - 13位点的母源印记基因表达失败。
通过多种渠道，我们试图识别出居住在英国一个健康区域内的所有PWS患者。在其他区域识别出的额外PWS患者也被招募进来以扩大研究样本。还确定了一组因PWS以外病因导致LD的对照组。这三组中所有三岁以上且同意参与的人，都接受了能力和学业测试评估。此外，他们的主要照顾者接受了半结构化访谈。从所有同意参与的参与者那里采集了用于基因诊断的血样。
总体样本的智商分布大致呈正态分布，平均智商比普通人群低40分。两种主要遗传亚型之间存在系统性差异。二体患者在认知特征上与缺失患者及对照组LD人群（后两组非常相似）不同，前者语言能力较好但编码能力受损。一些患有PWS缺失的患者具有较强的视觉空间技能。
我们认为，智商呈正态分布但相对于普通人群向下偏移，是PWS基因对智商产生整体影响的结果，而在15号染色体母源二体患者中观察到的不同认知特征，是15号染色体上一个或多个基因的特定效应，这些基因在二体患者中相对于缺失患者有差异表达或不表达。一种假设是，这些细微的认知差异是性别特异性印记基因对大脑偏侧化的遗传影响的表现。这需要进一步研究。
