Verlander P C, Kaporis A, Liu Q, Zhang Q, Seligsohn U, Auerbach A D
Laboratory of Human Genetics and Hematology, Rockefeller University, New York, NY 10021-6399, USA.
Blood. 1995 Dec 1;86(11):4034-8.
Fanconi anemia (FA) is a genetically and phenotypically heterogeneous autosomal recessive disorder defined by a cellular hypersensitivity to DNA cross-linking agents. One of the FA genes, FAC, has been cloned and the genomic structure of the coding region has been characterized. We have developed amplification refractory mutation system (ARMS) assays for five known mutations in FAC, and have applied these assays to determine the carrier frequency of the IVS4 + 4 A-->T (IVS4) mutation in an Ashkenazi Jewish population. We tested 3,104 Jewish individuals, primarily of Ashkenazi descent, for the two most common FAC mutations, IVS4 and 322delG. Thirty-five IVS4 carriers were identified, for a carrier frequency of 1 in 89 (1.1%; 95% confidence interval 0.79% to 1.56%); no 322delG carriers were found. To determine if the IVS4 mutation was confined to the Ashkenazi Jewish population, we tested 563 Iraqi Jews for IVS4, and no carriers were found. Because the IVS4 mutation has only been found on chromosomes of Ashkenazi Jewish origin and is the only FAC mutation found on these chromosomes, we suggest that a founder effect is responsible for the high frequency of this mutation. With a carrier frequency greater than 1% and simple testing available, the IVS4 mutation merits inclusion in the battery of tests routinely provided to the Jewish population.
范可尼贫血（FA）是一种遗传性和表型异质性的常染色体隐性疾病，其特征为细胞对DNA交联剂高度敏感。FA基因之一FAC已被克隆，其编码区的基因组结构也已明确。我们针对FAC基因中的五个已知突变开发了扩增阻滞突变系统（ARMS）检测方法，并应用这些方法来确定阿什肯纳兹犹太人群中IVS4 + 4 A→T（IVS4）突变的携带频率。我们检测了3104名主要为阿什肯纳兹血统的犹太个体，以查找两种最常见的FAC突变，即IVS4和322delG。共鉴定出35名IVS4突变携带者，携带频率为1/89（1.1%；95%置信区间为0.79%至1.56%）；未发现322delG突变携带者。为确定IVS4突变是否仅局限于阿什肯纳兹犹太人群，我们检测了563名伊拉克犹太人的IVS4突变，未发现携带者。由于IVS4突变仅在阿什肯纳兹犹太裔来源的染色体上被发现，且是这些染色体上唯一发现的FAC突变，我们认为该突变的高频率是由奠基者效应导致的。鉴于其携带频率大于1%且检测方法简便，IVS4突变应纳入常规为犹太人群提供的检测项目中。
