Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India
Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India
复制标题
DOI：
10.1111/j.1365-2516.2007.01477.x
复制
发表时间：
2007-07-01
期刊：
影响因子：
3.9
通讯作者：
Peyvandi, F.
中科院分区：
文献类型：
--
作者：
Jayandharan, G.;Spreafico, M.;Peyvandi, F.
FV和FVIII合并缺乏症（F5F8D）是一种罕见的常染色体隐性遗传病（1:1.00 .000），由编码FV和FVIII货物受体复合物的LMAN1或MCFD2基因缺陷引起。我们报告了9例不相关的FV和FVIII凝血剂活性低的印度患者的表型和基因型分析[FV:C，范围：5.6-22.4%和FVIII:C，范围：8.3-27.1%]。在所有9例患者中均发现4个纯合突变，包括2个帧移位，1个错义和1个剪接位点。其中，LMAN1的72 bp缺失（c.813_822 + 62del72, p.K272fs）、MCFD2的35 bp缺失（c.210_244del35）和MCFD2的缺失突变（p.D122V）（在4例患者中发现）是新的突变。先前报道的c.149 + 5G >在其余5例患者中鉴定出MCFD2的转变。p.E71fs和c.149 + 5G > A缺陷患者的MCFD2基因单倍型分析表明，这两种突变具有独立的起源。在9名患者中的7名患者中鉴定出MCFD2基因的两个常见突变（p.E71fs, c.149 + 5G > A），特别是c.149 + 5G > A（占患者的55.6%），表明该基因可能是该人群中F5F8D遗传诊断过程中首先分析的基因。这是第一份描述南印度血统的F5F8D患者一致数量的分子分析报告，该人群具有这种隐性出血性疾病的高频率。
Combined FV and FVIII deficiency (F5F8D) is a rare (1:1.000.000) autosomal recessive disorder caused by a defect in the LMAN1 or MCFD2 genes, encoding for a FV and FVIII cargo receptor complex. We report the phenotype and genotype analyses in nine unrelated Indian patients with low FV and FVIII coagulant activity [FV:C, range: 5.6-22.4% and FVIII:C, range: 8.3-27.1%]. Four homozygous mutations, including two frame shift, one missense and one splice site, were identified in all the nine patients. Three of them, a 72-bp deletion in LMAN1 (c.813_822 + 62del72, p.K272fs), a 35-bp deletion in MCFD2 (c.210_244del35) and a missence mutation in MCFD2 (p.D122V), identified in four patients, were novel mutations. A previously reported c.149 + 5G > A transition in MCFD2 was identified in the remaining five patients. Haplotype analysis of MCFD2 gene in patients with p.E71fs and c.149 + 5G > A defects suggested an independent origin of both these mutations. The identification of two common mutations (p.E71fs, c.149 + 5G > A) in MCFD2 gene in seven of nine patients, particularly the c.149 + 5G > A (55,6% of patients), suggests that this gene could be the first to be analysed during the genetic diagnosis of F5F8D in this population. This is the first report describing the molecular analysis of a consistent number of F5F8D patients of South Indian origin, a population with a high frequency of such recessive bleeding disorders.