Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome.
Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome.
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DOI：
10.1136/jmg.2008.063412
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发表时间：
2009-08
影响因子：
4
通讯作者：
de Vries BB
中科院分区：
文献类型：
--
作者：
van Bon BW;Mefford HC;Menten B;Koolen DA;Sharp AJ;Nillesen WM;Innis JW;de Ravel TJ;Mercer CL;Fichera M;Stewart H;Connell LE;Ounap K;Lachlan K;Castle B;Van der Aa N;van Ravenswaaij C;Nobrega MA;Serra-Juhé C;Simonic I;de Leeuw N;Pfundt R;Bongers EM;Baker C;Finnemore P;Huang S;Maloney VK;Crolla JA;van Kalmthout M;Elia M;Vandeweyer G;Fryns JP;Janssens S;Foulds N;Reitano S;Smith K;Parkel S;Loeys B;Woods CG;Oostra A;Speleman F;Pereira AC;Kurg A;Willatt L;Knight SJ;Vermeesch JR;Romano C;Barber JC;Mortier G;Pérez-Jurado LA;Kooy F;Brunner HG;Eichler EE;Kleefstra T;de Vries BB
重复的15q13.3微缺失最近用相同的近端（BP4）和远端（BP5）断点鉴定，并与轻度至中度的智力低下和癫痫有关。
为了进一步评估这种新颖的15q13.3微缺失综合征的临床意义，具有缺失的18个新概率是分子和临床表征的。此外，我们评估了BP3和BP4之间近端缺失的家族的特征。最后，在本研究中包括四名BP3-BP4-BP5区域中重复的患者，以确定该区域重复的临床意义。
我们系列中的15q13.3微骨骼与高度可变的室内和室间表型有关。在确定的18个删除中，至少有11个继承了。此外，来自四个不同家庭的10个兄弟姐妹中的7个也有这种缺失：一个有轻度的发育延迟，四个在童年时期只有学习问题，但在成年人的日常生活中运作良好，而另外两个人根本没有学习问题。与以前的发现相反，癫痫发作并不是我们系列的共同特征（只有17个生活证据中的2个）。三名缺失的患者患有心脏缺陷和位于关键区域的KLF13基因的缺失，可能会导致这些异常。近端BP3-BP4缺失的单个家族的有限数据表明，这种缺失可能没有临床意义。 BP3-BP4-BP5区域重复的患者没有具有可识别的表型，但在4例患者中有2例中发现了精神病。
总体而言，我们的发现扩大了与15q13.3缺失相关的表型频谱，并表明在某些人中，15q13.3的缺失不足以引起疾病。与不可预测且可变的表型结局相关的微骨骼综合征的存在将使临床医生在诊断困难中构成临床医生，并在诊断环境中挑战常用的范式，即从表型上正常父母继承的畸变通常没有临床后果。
Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. To further assess the clinical implications of this novel 15q13.3 microdeletion syndrome, eighteen new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. The 15q13.3 microdeletion in our series was associated with a highly variable intra- and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognizable phenotype, but psychiatric disease was noted in 2 of 4 patients. Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with diagnostic difficulties and challenge the commonly used paradigm in the diagnostic setting that aberrations inherited from a phenotypically normal parent are usually without clinical consequences.
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影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
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