Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
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DOI：
10.1136/jmg.2008.058701
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发表时间：
2008-11
影响因子：
4
通讯作者：
de Vries BB
中科院分区：
文献类型：
--
作者：
Koolen DA;Sharp AJ;Hurst JA;Firth HV;Knight SJ;Goldenberg A;Saugier-Veber P;Pfundt R;Vissers LE;Destrée A;Grisart B;Rooms L;Van der Aa N;Field M;Hackett A;Bell K;Nowaczyk MJ;Mancini GM;Poddighe PJ;Schwartz CE;Rossi E;De Gregori M;Antonacci-Fulton LL;McLellan MD 2nd;Garrett JM;Wiechert MA;Miner TL;Crosby S;Ciccone R;Willatt L;Rauch A;Zenker M;Aradhya S;Manning MA;Strom TM;Wagenstaller J;Krepischi-Santos AC;Vianna-Morgante AM;Rosenberg C;Price SM;Stewart H;Shaw-Smith C;Brunner HG;Wilkie AO;Veltman JA;Zuffardi O;Eichler EE;de Vries BB
染色体17q21.31微缺失综合征是一种新型基因组疾病，最初是通过对不明原因智力低下患者进行高分辨率基因组分析发现的。我们报告了22例17q21.31微缺失综合征患者的分子和/或临床特征。我们估计该综合征的患病率为1/16000，并表明它是高度诊断不足。广泛的临床检查显示，发育迟缓，肌张力减退，面部畸形，包括长脸，管状或梨形鼻子和球状鼻尖，以及友好/和蔼可亲的行为是最典型的特征。其他临床重要特征包括癫痫、心脏缺陷和肾脏/泌尿系统异常。使用高分辨率的寡核苷酸阵列，我们缩小17q21.31的关键区域的424 kb的基因组片段（chr 17：41046729-41470954，hg 17），包括至少6个基因，其中是编码微管相关蛋白tau（MAPT）的基因。在122名具有17q21.31缺失携带者的表型但不携带复发性缺失的个体中进行MAPT突变筛查，未能鉴定出任何疾病相关变体。在5个缺失携带者中，我们在L2 LINE基序内包含的近端断裂点处鉴定出<500 bp的重排热点，并表明在每种情况下，检测到的产生缺失的亲本携带共同的900 kb 17q21.31倒位多态性，表明这种倒位是缺失发生的必要因素（p<10-5）。我们的数据建立了17q21.31微缺失综合征作为一种临床和分子识别良好的基因组疾病。
The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. We estimate the prevalence of the syndrome to be 1 in 16 000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729–41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10–5). Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.
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影响因子：
30.8
作者：
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通讯作者：
Eichler, Evan E.
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