Haematology Department, Hospital Universitario La Paz, Madrid, Spain.
Thromb Haemost. 2010 Oct;104(4):718-23. doi: 10.1160/TH10-02-0085. Epub 2010 Jul 20.
Severe manifestations of X-linked recessive disorders such as haemophilia A (HA) are rare in females. Here we describe the clinical and genetic findings in five female HA patients from two different Spanish families. Three sisters born to consanguineous parents presented moderate bleeding due to a known mutation (p.Ser1791Pro) detected in a homozygous state. In the second family, two sisters with Morris syndrome (46,XY) and mild/moderate illness were hemizygous for a novel missense mutation, p.Phe2127Ser. The mutation is predicted to impair binding to the factor VIII (FVIII) carrier protein, von Willebrand factor, and thus increased clearance of FVIII from plasma. Clinical and molecular characterisation of these patients is essential to optimise follow-up, genetic counselling and treatment of the disease.
X 连锁隐性遗传病如血友病 A（HA）的严重表现形式在女性中较为罕见。本研究描述了来自两个不同西班牙家族的五名女性 HA 患者的临床和遗传学发现。三名同胞姐妹因已知突变（p.Ser1791Pro）纯合状态而表现出中度出血，该突变已被检出。在第二个家族中，两名患有 Morris 综合征（46,XY）和轻度/中度疾病的姐妹为杂合子，携带一种新的错义突变 p.Phe2127Ser。该突变预计会损害与 FVIII 载体蛋白、血管性血友病因子的结合，从而增加 FVIII 从血浆中的清除率。对这些患者进行临床和分子特征分析对于优化疾病的随访、遗传咨询和治疗至关重要。
