Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India

G. Jayandharan, M. Spreafico, A. Viswabandya, M. Chandy, A. Srivastava, Flora Peyvandi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)413-419
Number of pages7
JournalHaemophilia
Volume13
Issue number4
DOIs
Publication statusPublished - Jul 2007

Keywords

  • Combined FV and FVIII deficiency
  • F5F8D
  • India
  • LMAN1
  • MCFD2
  • Mutation

ASJC Scopus subject areas

  • Hematology

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