El-Maarri Osman, Singer Heike, Klein Claudia, Watzka Matthias, Herbiniaux Ursula, Brackmann Hans H, Schröder Jörg, Graw Jochen, Müller Clemens R, Schramm Wolfgang, Schwaab Rainer, Haaf Thomas, Hanfland Peter, Oldenburg Johannes
Institute of Experimental Hematology and Transfusion Medicine, Sigmund Freud Str 25, 53127 Bonn, Germany.
Blood. 2006 Apr 1;107(7):2759-65. doi: 10.1182/blood-2005-09-3702. Epub 2005 Dec 8.
Hemophilia A (HA) is caused by partial or total deficiency of F8 protein activity. In a small group, about 1.8% of patients with HA, no mutation is found in the F8 gene. Among this group, we report here on one patient with severe HA in whom no mRNA of the F8 gene was detected. Using 2 common polymorphisms in F8 exon 14, we were able to show that the same allele shared by the patient, his mother, and his sister was not detected by reverse transcription-polymerase chain reaction (RT-PCR) from total blood mRNA. Skewed X-chromosome inactivation in both the mother and the sister was excluded by studying the methylation profile of the androgen receptor gene (HUMARA locus). These findings strongly suggest that the cause of HA in this patient is either absence or rapid degradation of the F8 mRNA, which points to a novel mechanism leading to HA.
甲型血友病（HA）是由F8蛋白活性部分或完全缺乏引起的。在一小部分人中，约1.8%的HA患者在F8基因中未发现突变。在这组患者中，我们在此报告一名严重HA患者，其F8基因的mRNA未被检测到。利用F8外显子14中的2个常见多态性，我们能够证明，通过对全血mRNA进行逆转录-聚合酶链反应（RT-PCR），未检测到该患者与其母亲和妹妹共有的相同等位基因。通过研究雄激素受体基因（HUMARA位点）的甲基化谱，排除了母亲和妹妹中X染色体失活偏倚的情况。这些发现强烈表明，该患者HA的病因是F8 mRNA缺失或快速降解，这指向了一种导致HA的新机制。
