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A novel genetic variant in DNAI2 detected by custom gene panel in a newborn with Primary Ciliary Dyskinesia: case report
BMC Medical Genetics Pub Date : 2020-11-10 , DOI: 10.1186/s12881-020-01160-5
Maria Santa Rocca , Gioia Piatti , Angela Michelucci , Raffaella Guazzo , Veronica Bertini , Cinzia Vinanzi , Maria Adelaide Caligo , Angelo Valetto , Carlo Foresta

Primary ciliary dyskinesia (PCD) is a highly heterogeneous genetic disorder caused by defects in motile cilia. The hallmark features of PCD are the chronic infections of the respiratory tract, moreover, clinical manifestations include also laterality defects and risk of male infertility. Clinical phenotypes of PCD are the result of mutations in genes encoding components of axonema or factors involved in axonemal assembly. Recent studies have identified over 45 PCD-associated genes, therefore, molecular analysis represents a powerful diagnostic tool to confirm and uncover new genetic causes of this rare disease. Here, we describe a female infant of Moroccan origin with normal pressure hydrocephalus (NPH) in addition to most common PCD symptoms. Transmission Electron Microscopy (TEM) and molecular tests, such as a Next generation Sequencing panel and a custom array CGH, were performed for diagnosis of PCD. TEM revealed outer dynein arm (ODA) defects, whilst molecular analyses detected a novel 6,9 kb microdeletion in DNAI2 gene. Since DNAI2 mutations are very rare, this case report contributes to better delineate the important role of DNAI2 as causative of PCD phenotype, suggesting, furthermore, that the variations in DNAI2 may be as a new genetic risk factor for NPH. Indeed, although the association of hydrocephalus with PCD has been well documented, however, only a small number of human patients show this defect. Furthermore, this study highlights the importance of high-throughput technologies in advancing our understanding of heterogeneous genetic disorders.

中文翻译:

通过定制基因组在新生儿原发性睫状运动障碍中检测到一种新型的DNAI2基因变异:病例报告

原发性睫状运动障碍(PCD)是由运动性纤毛缺陷引起的高度异质性遗传疾病。PCD的标志性特征是呼吸道的慢性感染,此外,临床表现还包括偏侧性缺陷和男性不育的风险。PCD的临床表型是编码轴突成分或涉及轴突装配的因子的基因突变的结果。最近的研究已经鉴定出超过45种与PCD相关的基因,因此,分子分析代表了一种强大的诊断工具,可以确认和揭示这种罕见疾病的新遗传原因。在这里,我们描述了除最常见的PCD症状外,患有摩洛哥血统正常的脑积水(NPH)的女婴。透射电子显微镜(TEM)和分子测试,进行了诸如下一代测序面板和定制阵列CGH之类的诊断PCD。透射电镜显示了达因臂的外部缺陷(ODA),而分子分析检测到DNAI2基因中有一个新的6,9 kb微缺失。由于DNAI2突变非常罕见,因此本病例报告有助于更好地描述DNAI2作为PCD表型病因的重要作用,并进一步暗示DNAI2的变异可能是NPH的新遗传危险因素。确实,尽管脑积水与PCD的关联已有充分的文献记载,但是,只有少数人类患者显示出这种缺陷。此外,本研究强调了高通量技术在增进我们对异质遗传疾病的理解中的重要性。透射电镜显示了达因臂的外部缺陷(ODA),而分子分析检测到DNAI2基因中有一个新的6,9 kb微缺失。由于DNAI2突变非常罕见,因此本病例报告有助于更好地描述DNAI2作为PCD表型病因的重要作用,并进一步暗示DNAI2的变异可能是NPH的新遗传危险因素。确实,尽管脑积水与PCD的关联已有充分的文献记载,但是,只有少数人类患者显示出这种缺陷。此外,本研究强调了高通量技术在增进我们对异质遗传疾病的理解中的重要性。透射电镜显示了达因臂的外部缺陷(ODA),而分子分析检测到DNAI2基因中有一个新的6,9 kb微缺失。由于DNAI2突变非常罕见,因此本病例报告有助于更好地描述DNAI2作为PCD表型病因的重要作用,并进一步暗示DNAI2的变异可能是NPH的新遗传危险因素。确实,尽管脑积水与PCD的关联已有充分的文献记载,但是,只有少数人类患者显示出这种缺陷。此外,本研究强调了高通量技术在增进我们对异质遗传疾病的理解中的重要性。该病例报告有助于更好地描述DNAI2作为PCD表型病因的重要作用,并进一步暗示DNAI2的变异可能是NPH的新遗传危险因素。确实,尽管脑积水与PCD的关联已有充分的文献记载,但是,只有少数人类患者显示出这种缺陷。此外,本研究强调了高通量技术在增进我们对异质遗传疾病的理解中的重要性。该病例报告有助于更好地描述DNAI2作为PCD表型病因的重要作用,并进一步暗示DNAI2的变异可能是NPH的新遗传危险因素。确实,尽管脑积水与PCD的关联已有充分的文献记载,但是,只有少数人类患者显示出这种缺陷。此外,本研究强调了高通量技术在增进我们对异质遗传疾病的理解中的重要性。
更新日期:2020-11-12
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