Cognitive profile in a large french cohort of adults with Prader-Willi syndrome: differences between genotypes
Cognitive profile in a large french cohort of adults with Prader-Willi syndrome: differences between genotypes
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DOI：
10.1111/j.1365-2788.2010.01251.x
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发表时间：
2010-03-01
影响因子：
3.6
通讯作者：
Thuilleaux, D.
中科院分区：
文献类型：
--
作者：
Copet, P.;Jauregi, J.;Thuilleaux, D.
研究背景Prader-Willi综合征(PWS)是一种罕见的遗传性疾病，其特征是发育异常导致躯体和心理症状。这些症状包括畸形特征、发育和性成熟受损、吞噬过多、智力迟缓、学习障碍和适应不良行为。PWS是由于位于15q11-13染色体区域的母系印记基因缺乏表达所致。其原因是70%的病例是父系染色体的新缺失，25%的病例是母系单亲二体。这两种主要的基因类型表现出不同，特别是在认知和行为特征上，但机制尚不清楚。这项研究评估了一组遗传确诊的PWS成人的认知障碍，分析了他们的认知优势和弱点，并从基因类型的角度进行了比较。方法99名成年男性和女性，所有患者都在一个多学科护理的专科病房住院。韦氏成人智力量表(WAIS-III)由同一心理学家在相同条件下对所有患者进行测试。85名患者能够应对测试情况。采用非参数统计工具对他们的得分进行分析。探讨其与性别、年龄、体重指数的相关性。结果总队列中智商分布呈非正态分布，中位数如下：全量智商(FSIQ)：52.0(Q1：46.0；Q3：60.0)；言语智商(VIQ)：53.0(Q1：48；Q3：62)；操作智商(PIQ)：52.5(Q1：48；Q3：61)。未发现与性别、年龄或体重指数相关。组间比较，FSIQ和VIQ差异无统计学意义。缺失组的PIQ得分显著高于缺失组。总队列和缺失组呈VIQ=PIQ分布，而非缺失组VIQ和PIQ为VIQ和PIQ。两组分测验成绩有显著差异，删除组在物体组装、图片排列和数字符号编码三个分测验中得分较高。一些相对的优势和劣势涉及整个队列，但其他的只涉及一种基因类型。讨论我们记录了一大批法国PWS患者的全球智力损害。这些分数略低于大多数其他研究报告的分数。我们的数据证实了之前发表的两种主要PWS基因在认知方面的差异，并为支持这一假说提供了新的证据。这些结果可能会指导未来的神经心理学研究，以确定PWS的认知加工。这些知识对于提高我们对基因-大脑-行为关系的理解以及为治疗和教育项目开辟新的视角至关重要。
BackgroundPrader-Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of expression of maternally imprinted genes situated in the 15q11-13 chromosome region. The origin is a 'de novo' deletion in the paternal chromosome in 70% of the cases and a maternal uniparental disomy in 25%. The two main genotypes show differences, notably regarding cognitive and behavioural features, but the mechanisms are not clear. This study assessed cognitive impairment in a cohort of adults with genetically confirmed PWS, analysed their profiles of cognitive strengths and weaknesses, and compared the profiles in terms of genotype.MethodsNinety-nine male and female adults participated, all inpatients on a specialised unit for the multidisciplinary care of PWS. The Wechsler Adult Intelligence Scale (WAIS-III) was administered to all patients in identical conditions by the same psychologist. Eighty-five patients were able to cope with the test situation. Their scores were analysed with non-parametric statistical tools. The correlations with sex, age and body mass index were explored. Two genotype groups were compared: deletion (n = 57) and non-deletion (n = 27).ResultsThe distribution of intelligence quotients in the total cohort was non-normal, with the following values (medians): Full Scale Intelligence Quotient (FSIQ): 52.0 (Q1:46.0; Q3:60.0), Verbal Intellectual Quotient (VIQ): 53.0 (Q1:48; Q3:62) and Performance Intellectual Quotient (PIQ): 52.5 (Q1:48; Q3:61). No correlation was found with sex, age or body mass index. Comparison between groups showed no significant difference in FSIQ or VIQ. PIQ scores were significantly better in the deletion group. The total cohort and the deletion group showed the VIQ = PIQ profile, whereas VIQ > PIQ was observed in the non-deletion group. The subtest scores in the two groups showed significant differences, with the deletion group scoring better in three subtests: object assembly, picture arrangement and digit symbol coding. Some relative strengths and weaknesses concerned the total cohort, but others concerned only one genotype.DiscussionWe documented a global impairment in the intellectual abilities of a large sample of French PWS patients. The scores were slightly lower than those reported in most other studies. Our data confirmed the previously published differences in the cognitive profiles of the two main PWS genotypes and offer new evidence to support this hypothesis. These results could guide future neuropsychological studies to determine the cognitive processing in PWS. This knowledge is essential to improve our understanding of gene-brain-behaviour relationships and to open new perspectives on therapeutic and educational programmes.