title: Mutations in the MCFD2 gene and a novel mutation in the LMAN1 gene in Indian families with combined deficiency of factor V and VIII.
abstract: Combined deficiency of factors V (FV) and factor VIII (FVIII) (F5F8D) is an autosomal recessive bleeding disorder caused by simultaneous moderate-to-mild decrease of both clotting proteins. Mutations in two components of the ER-Golgi intermediate compartment (ERGIC-53), i.e., lectin mannose binding protein (LMAN1) and multiple coagulation factor deficiency 2 (MCFD2), have been found to be responsible for this dual deficiency in most of the cases reported in literature. Three Indian families with F5F8D were analyzed for the presence of mutations in their LMAN1 and MCFD2 genes. One of the three families showed the presence of a G to A substitution in exon 2 of the MCFD2 gene, whereas another family showed a nonsense mutation, i.e., G to T substitution, in exon 2 of the LMAN1 gene, the latter being a novel mutation not previously reported. The third family did not show mutations in either of the two genes, suggesting that a significant subset of F5F8D cases may be due to additional genes resulting in a similar phenotype.
authors.affiliation: Haemostasis Laboratory, Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Mohanty
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
authors.forename: Marta
authors.initials: M
authors.lastname: Spreafico
authors.forename: Isabella
authors.initials: I
authors.lastname: Garagiola
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D005091:Exons; D005166:Factor V Deficiency / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D037241:Mannose-Binding Lectins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; C084004:LMAN1 protein, human; C475146:MCFD2 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins