Williams syndrome.
Williams syndrome.
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DOI：
10.1038/s41572-021-00276-z
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发表时间：
2021-06-17
影响因子：
81.5
通讯作者：
Pober, Barbara R.
中科院分区：
文献类型：
--
作者：
Kozel, Beth A.;Barak, Boaz;Kim, Chong Ae;Mervis, Carolyn B.;Osborne, Lucy R.;Porter, Melanie;Pober, Barbara R.
威廉姆斯综合症（WS）是一种相对罕见的微缺失症，发病率高达1:7 500。它是由于在减数分裂中低拷贝DNA重复元件的错配而产生的。大多数WS患者的缺失大小相似，导致7q11.23染色体上25-27个基因的一个拷贝丢失。由此产生的独特疾病影响多个系统，其主要特征包括但不限于心血管疾病（特征性的大动脉狭窄，最明显的是瓣上主动脉狭窄），独特的颅面外观和特定的认知和行为特征，包括智力残疾和过度社交。基因型-表型证据最明显的是弹性蛋白（ELN）基因，它负责WS的血管和结缔组织特征，以及转录因子基因GTF2I和GTF2IRD1，它们已知会影响智力、社交功能和焦虑。越来越多的证据也将表型后果归因于BAZ1B、LIMK1、STX1A和MLXIPL的缺失，但需要更多的工作来了解这些缺失对临床结果的影响机制。在世界上技术进步的地区，诊断年龄已经下降，如染色体微阵列，使临床医生能够在没有正式怀疑的情况下诊断WS，从而允许医学和发展专家进行早期干预。WS的所有主要特征都具有相当大的表型变异性，但这种变异性的具体来源尚不清楚。进一步调查以确定造成这些差异的因素可能导致基于机制而不是基于症状的治疗，因此应该是一个高度优先的研究。
Williams syndrome (WS) is a relatively rare microdeletion disorder that occurs in as many as 1:7,500 individuals. It arises due to mispairing of low-copy DNA repetitive elements at meiosis. Deletion size is similar across most individuals with WS and leads to loss of one copy of 25–27 genes on chromosome 7q11.23. The resulting unique disorder affects multiple systems, with cardinal features including, but not limited to, cardiovascular disease (characteristically stenosis of the great arteries and most notably supravalvar aortic stenosis), a distinctive craniofacial appearance and a specific cognitive and behavioural profile that includes intellectual disability and hypersociability. Genotype–phenotype evidence is strongest for the elastin (ELN) gene, which is responsible for the vascular and connective tissue features of WS, and for the transcription factor genes GTF2I and GTF2IRD1, which are known to affect intellectual ability, social functioning and anxiety. Mounting evidence also ascribes phenotypic consequences to deletion of BAZ1B, LIMK1, STX1A and MLXIPL, but more work is needed to understand the mechanism by which these deletions contribute to clinical outcomes. Age of diagnosis has fallen in regions of the world where technological advances, such as chromosomal microarray, enable clinicians to make the diagnosis of WS without formally suspecting it, allowing earlier intervention by medical and developmental specialists. Phenotypic variability is considerable for all cardinal features of WS, but the specific sources of this variability remain unknown. Further investigation to identify factors responsible for these differences may lead to mechanism-based rather than symptom-based therapies and, therefore, should be a high research priority.
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影响因子：
1.8
作者：
Dutra RL;Honjo RS;Kulikowski LD;Fonseca FM;Pieri PC;Jehee FS;Bertola DR;Kim CA
通讯作者：
Kim CA
影响因子：
25
作者：
Barak, Boaz;Zhang, Zicong;Feng, Guoping
通讯作者：
Feng, Guoping
影响因子：
12.4
作者：
Borralleras, Cristina;Sahun, Ignasi;Campuzano, Victoria
通讯作者：
Campuzano, Victoria
影响因子：
3.8
作者：
Becerra, Angela M.;Mervis, Carolyn B.
通讯作者：
Mervis, Carolyn B.
影响因子：
6.1
作者：
Bouchireb, Karim;Boyer, Olivia;Salomon, Remi
通讯作者：
Salomon, Remi