TY - JOUR
T1 - Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India
AU - Jayandharan, G.
AU - Spreafico, M.
AU - Viswabandya, A.
AU - Chandy, M.
AU - Srivastava, A.
AU - Peyvandi, Flora
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Combined FV and FVIII deficiency
KW - F5F8D
KW - India
KW - LMAN1
KW - MCFD2
KW - Mutation
UR - http://www.scopus.com/inward/record.url?scp=34447293733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447293733&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2516.2007.01477.x
DO - 10.1111/j.1365-2516.2007.01477.x
M3 - Article
C2 - 17610559
AN - SCOPUS:34447293733
VL - 13
SP - 413
EP - 419
JO - Haemophilia
JF - Haemophilia
SN - 1351-8216
IS - 4
ER -