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Tectonic gene mutations in patients with Joubert syndrome

机译:Joubert综合征患者的构造基因突变

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So far very few patients with sequence variants in the closely related tectonic genes TCTN1-3 have been described. By multi-gene panel next-generation sequencing (NGS) in patients with Joubert syndrome, we identified two more patients and summarize what is currently known about the phenotypes associated with sequence variants in these genes. In a boy aged 12 years with intellectual disability and the classical molar tooth sign on MRI, a homozygous splice-site sequence variant in TCTN3 leading to in-frame skipping of exon 7 was detected. A previously described non-truncating sequence variant in TCTN3 was also associated with Joubert syndrome, whereas four truncating sequence variants were detected in patients with Meckel-Gruber or Mohr-Majewski syndrome. The second patient, a boy aged 7 years with severe psychomotor retardation, was found to carry a homozygous canonic splice-site sequence variant in TCTN2. So far, only three sequence variants associated with Joubert syndrome and two with Meckel-Gruber syndrome have been described in this gene. Reviewing the clinical data on patients with sequence variants in the tectonic genes TCTN1-3 reveals that all of them have a neurological phenotype with vermis hypoplasia or occipital encephalocele associated with severe intellectual disability in the surviving patients. In contrast, other features frequently seen in patients with ciliopathies such as nephronophthisis, liver fibrosis, retinal dystrophy or coloboma have not been reported. Our patients emphasize the usefulness and efficacy of a comprehensive NGS panel approach. A concise genetic diagnosis may help to prevent unnecessary investigations and improve the clinical management of these patients.
机译:迄今为止,很少有人描述了在紧密相关的构造基因TCTN1-3中具有序列变异的患者。通过Joubert综合征患者的多基因专家组下一代测序(NGS),我们确定了另外两名患者,并总结了目前已知的与这些基因中的序列变异相关的表型。在一个12岁的智障男孩和MRI上的经典磨牙迹象的男孩中,检测到TCTN3中的纯合剪接位点序列变异,导致框内跳过第7外显子。先前在TCTN3中描述的非截短序列变异体也与Joubert综合征相关,而在Meckel-Gruber或Mohr-Majewski综合征患者中检测到四个截短序列变异体。第二例患者是一个7岁的男孩,患有严重的精神运动发育迟缓,被发现在TCTN2中携带纯合的经典剪接位点序列变异。迄今为止,在该基因中仅描述了与乔伯特综合征相关的三个序列变体和两个与梅克尔-格鲁伯综合征相关的序列变体。审查有关构造基因TCTN1-3中具有序列变异的患者的临床数据后发现,所有患者均具有神经表型,并伴有ver瘤发育不全或枕叶脑膨出,与尚存患者的严重智力障碍有关。相反,尚未报道在患有纤毛病的患者中经常见到的其他特征,例如肾炎,肝纤维化,视网膜营养不良或淋巴瘤。我们的患者强调了全面的NGS专家组方法的有用性和有效性。简明的遗传学诊断可能有助于防止不必要的研究并改善这些患者的临床管理。

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