Laboratorio de Citogenomica, Departamento de Patologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR.
Clinics (Sao Paulo). 2017 Oct;72(9):526-537. doi: 10.6061/clinics/2017(09)02.
The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients.
We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays.
Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes.
The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.
人类基因组包含多种类型的变异，如拷贝数变异，这些变异可导致特定的临床异常。不同的技术用于检测这些变化，获得明确的诊断对于理解疾病的病理生理学非常重要。本研究的目的是评估多重连接依赖探针扩增和阵列技术在综合征患者病因诊断中的诊断能力。
我们使用多重连接依赖探针扩增和阵列分析了 93 例发育迟缓伴多发先天畸形患者。
使用不同试剂盒的多重连接依赖探针扩增显示约 33.3%的患者存在多种变化。使用不同平台的阵列检测到至少一种致病性变化的检出率约为 53.75%，良性变化的检出率为 46.25%。两种技术的同时评估显示，一致性约为 97.8%，尽管在所有情况下结果并不相同。与阵列结果相反，MLPA 技术检测到约 70.6%的致病性变化。
所得结果与文献报道的数据相符，但由于选择患者的标准不同，总检出率高于以往报道的检出率。虽然阵列是诊断最有效的工具，但由于其在发展中国家大规模使用的成本较高，并不总是适合作为一线诊断方法。因此，需要临床和实验室与熟练的技术人员合作，针对最有效的和有益的分子诊断目标患者。
