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Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India
Author(s) -
JAYANDHARAN G.,
SPREAFICO M.,
VISWABANDYA A.,
CHANDY M.,
SRIVASTAVA A.,
PEYVANDI F.
Publication year - 2007
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2007.01477.x
Subject(s) - missense mutation , genetics , mutation , haplotype , gene , medicine , genotype , population , biology , environmental health
Summary. 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.