263.4 kb deletion within the TCF4 gene consistent with Pitt-Hopkins syndrome, inherited from a mosaic parent with normal phenotype
263.4 kb deletion within the TCF4 gene consistent with Pitt-Hopkins syndrome, inherited from a mosaic parent with normal phenotype
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DOI：
10.1016/j.ejmg.2013.03.005
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发表时间：
2013-06-01
影响因子：
1.9
通讯作者：
Anastasiadou, Violetta
中科院分区：
文献类型：
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作者：
Kousoulidou, Ludmila;Tanteles, George;Anastasiadou, Violetta
皮特-霍普金斯综合征（PTHS）是一种罕见的神经发育遗传性疾病，由于与其他已知的遗传综合征相似，仍未得到充分诊断。其主要特征为严重智力障碍、呼吸过度、典型的面部完形、癫痫倾向，由TCF4单倍功能不全引起。我们报告了一名14岁的男孩，出生于健康的非近亲父母，具有PTHS谱表型，表现为中度至重度发育迟缓，严重语言迟缓和面部畸形。使用基于阵列的比较基因组杂交（array- cgh）和400K定制阵列进行遗传研究，发现TCF4基因有263.4 kb的缺失，删除了外显子4-9。亲本阵列- cgh分析也进行了，表明父本镶嵌相同的缺失。通过实时荧光定量PCR证实了其嵌合性。目前的报告描述了与PTHS表型相关的新的TCF4缺失。此外，据我们所知，这是第一个这样的缺失被证明是从临床未受影响的马赛克亲本遗传的病例。我们的研究结果强调了在这种情况下，父母检测对更准确、更集中的产前诊断的重要性。父亲嵌合的水平和组织特异性将是一个有趣的进一步研究方向。(C) 2013 Elsevier Masson SAS。版权所有。
Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental genetic disorder, remaining under-diagnosed due to similarities with other known genetic syndromes. It is mainly characterized by severe intellectual disability, overbreathing, a typical facial gestalt, tendency to epilepsy and is caused by TCF4 haploinsufficiency. We report on a 14-year old boy, born to healthy non-consanguineous parents, with a PTHS spectrum phenotype, presenting with moderate to severe developmental delay, severe speech delay and facial dysmorphism. Genetic investigation using array-based comparative genomic hybridization (array-CGH) with a 400K custom array, revealed a 263.4 kb deletion within the TCF4 gene, removing exons 4-9. Parental array-CGH analysis was also performed, indicating paternal mosaicism for the same deletion. The mosaicism was confirmed by Quantitative Real-Time PCR. The current report describes a new TCF4 deletion associated with a PTHS phenotype. Moreover, it is the first case to our knowledge, where such a deletion is shown to be inherited from a clinically unaffected mosaic parent. Our results highlight the importance of parental testing in this setting for more accurate and focused prenatal diagnosis. The level and tissue-specificity of mosaicism in the father would be an interesting direction for further studies. (C) 2013 Elsevier Masson SAS. All rights reserved.