Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
Ann Lab Med. 2012 Sep;32(5):380-4. doi: 10.3343/alm.2012.32.5.380. Epub 2012 Aug 13.
Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.
范可尼贫血症(FA)是一种罕见的遗传疾病,影响多个身体系统。遗传测试,包括产前测试,是许多临床病症诊断的前提。然而,FA 的遗传测试很复杂,因为通常有许多基因与它的发展有关,并且这些基因中的一些经常发现有大片段缺失、重复或序列变异。本研究描述了在韩国的一名患者及其家庭中成功进行 FA 的分子诊断和随后的产前诊断的遗传测试。我们分析了 FANCA、FANCC 和 FANCG 基因的所有外显子和侧翼区域,以确定突变并进行随后的产前诊断。进行了多重连接依赖性探针扩增分析,以检测 FANCA 基因中的大片段缺失或重复。分子分析显示 FANCA 基因中有两个突变:一个移码突变 c.2546delC 和一个新的剪接突变 c.3627-1G>A。FANCA 突变分别从父母那里遗传,c.2546delC 来自父亲,而 c.3627-1G>A 源自母亲。羊水细胞为 c.3627-1G>A 杂合子,表明胎儿未受影响。这是首例在韩国成功应用于患者分子诊断和随后 FA 产前诊断的遗传测试报告。