High frequency of T9 and CFTR mutations in children with idiopathic bronchiectasis
High frequency of T9 and CFTR mutations in children with idiopathic bronchiectasis
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DOI：
10.1136/jmg.40.7.530
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发表时间：
2003-07
影响因子：
4
通讯作者：
R. G. Ruf;J. Berkman;M. T. F. Wolf;P. Nurnberg;M. Gattas;Eva-Maria Ruf;V. Hyland;J. Kromberg;I. Glass;J. MacMillan;E. Otto;G. Nurnberg;B. Lucke;H. Hennies;F. Hildebrandt
中科院分区：
文献类型：
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作者：
R. G. Ruf;J. Berkman;M. T. F. Wolf;P. Nurnberg;M. Gattas;Eva-Maria Ruf;V. Hyland;J. Kromberg;I. Glass;J. MacMillan;E. Otto;G. Nurnberg;B. Lucke;H. Hennies;F. Hildebrandt
Williams综合征（WS, MIM 194050）是一种罕见的（发生率为1/ 20000）多系统疾病1，由7q11.23.2基因单倍不足引起。WS与面部畸形、瓣上主动脉瓣狭窄（SVAS）等心血管疾病、婴儿高钙血症和生长缺陷有关。WS受试者的全部智商（IQ）通常在50到60之间，具有独特的认知特征，其特点是相对较好的语言能力以及较低的空间和建设性组织水平。这种不同的能力模式被命名为“WS认知特征”（WSCP）超过95%的临床定义的WS患者从头缺失约1.5 Mb，断点聚集在WS区域两侧的两个高度同源区域几个基因已经在缺失区域中被定位，包括编码突触装置成分的syntaxin 1A (STX1A)11和编码复制因子C复合体亚基的RFC2 12。虽然ELN单倍体功能不全与WS的心血管和可能的结缔组织异常有关，但其他基因在该疾病其余临床特征中的作用尚不清楚。特别是，目前尚不清楚是哪个基因决定了WS患者的认知和人格特征。据报道，只有ELN和LIMK1缺失的患者表现出特征性的WSCP，通常没有智力低下，但对其他包含ELN和LIMK1 14的小缺失的患者的分析并未证实这些结果。Limk1缺陷小鼠在脊柱形态和突触功能上表现出明显的异常。他们还表现出空间学习能力和恐惧反应的改变编码细胞质连接蛋白CLIP-115的CYLN2基因16定位于神经元和小脑胶质的树突状板层体中。
Williams syndrome (WS, MIM 194050) is a rare (frequency 1/20 000) multisystemic disorder1 caused by haploinsufficiency of genes at 7q11.23.2–4 WS is associated with dysmorphic facial features, supravalvular aortic stenosis (SVAS) and other cardiovascular diseases, infantile hypercalcaemia, and growth deficiency. The full intelligence quotient (IQ) of WS subjects is usually in the 50s to 60s, with a unique cognitive profile, characterised by relatively good verbal abilities alongside a low level of spatial and constructive organisation.5–7 This different pattern of abilities has been named the “WS cognitive profile” (WSCP).8 More than 95% of clinically defined WS patients have a de novo deletion of about 1.5 Mb, with the breakpoints clustered within two highly homologous regions flanking the WS region.9 Several genes have been mapped within the deleted region,10 including syntaxin 1A ( STX1A )11 that codes for a component of the synaptic apparatus, and RFC2 12 that encodes a subunit of the replication factor C complex. While ELN haploinsufficiency has been associated with the cardiovascular and possibly connective tissue abnormalities of WS,13 the role of other genes in the remaining clinical features of the disease is not known. In particular, it is not clear which gene(s) is responsible for the cognitive and personality profile characteristic of WS patients. It has been reported8 that patients with deletions of only ELN and LIMK1 show the characteristic WSCP, generally without mental retardation, but analysis of additional patients harbouring small deletions involving ELN and LIMK1 14 did not confirm these results. Limk1 deficient mice exhibit significant abnormalities in spine morphology and synaptic function. They also show altered spatial learning and fear response.15 The CYLN2 gene, coding for the cytoplasmic linker protein CLIP-115,16 localised in the dendritic lamellar bodies of neurones and cerebellar glia …