Jedrzejowska Maria, Borkowska Janina, Zimowski Janusz, Kostera-Pruszczyk Anna, Milewski Michał, Jurek Marta, Sielska Danuta, Kostyk Ewa, Nyka Walenty, Zaremba Jacek, Hausmanowa-Petrusewicz Irena
Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Eur J Hum Genet. 2008 Aug;16(8):930-4. doi: 10.1038/ejhg.2008.41. Epub 2008 Mar 12.
In this report, we present three families in which we identified asymptomatic carriers of a homozygous absence of the SMN1 gene. In the first family, the bialleleic deletion was found in three of four siblings: two affected brothers (SMA type 3a and 3b) and a 25-years-old asymptomatic sister. All of them have four SMN2 copies. In the second family, four of six siblings are affected (three suffer from SMA2 and one from SMA3a), each with three SMN2 copies. The clinically asymptomatic 47-year-old father has the biallelic deletion and four SMN2 copies. In the third family, the biallelic SMN1 absence was found in a girl affected with SMA1 and in her healthy 53-years-old father who had five SMN2 copies. Our findings as well as those of other authors show that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one.
在本报告中，我们展示了三个家族，在这些家族中我们鉴定出了SMN1基因纯合缺失的无症状携带者。在第一个家族中，在四个兄弟姐妹中的三个身上发现了双等位基因缺失：两个患病兄弟（3a型和3b型脊髓性肌萎缩症）和一个25岁的无症状姐妹。他们都有4个SMN2拷贝。在第二个家族中，六个兄弟姐妹中有四个患病（三个患有2型脊髓性肌萎缩症，一个患有3a型脊髓性肌萎缩症），每人有3个SMN2拷贝。临床无症状的47岁父亲有双等位基因缺失和4个SMN2拷贝。在第三个家族中，在一名患有1型脊髓性肌萎缩症的女孩及其健康的53岁父亲身上发现了双等位基因SMN1缺失，其父亲有5个SMN2拷贝。我们的发现以及其他作者的发现表明，双等位基因SMN1缺失的健康携带者中SMN2拷贝数增加是一个重要的脊髓性肌萎缩症表型修饰因子，但可能不是唯一的修饰因子。
