Utility of an exon 14 BslI polymorphism for improved genetic diagnosis of hemophilia A in Indian population.
BACKGROUND
Hemophilia A is a common X-linked recessive bleeding disorder caused by deleterious mutations in the gene encoding factor VIII. Though direct mutation analysis is the common practice in most of the developed countries, restriction fragment length polymorphism (RFLP) analysis using common polymorphic markers of factor VIII gene is still the most practical and feasible method in developing countries like India.


METHODS
We investigated the utility of a BslI polymorphism (A3864C) in exon 14 of factor VIII gene for the genetic diagnosis of hemophilia A families by polymerase chain reaction (PCR) followed by digestion with enzyme BslI.


RESULTS
Out of 213 unrelated women examined for heterozygosity of this marker, 69 were found to be informative (32.4%), with frequencies of 0.32 and 0.68 for the '+ ' and '- ' alleles respectively. Subsequently 13 hemophilia A families, which were not informative with any of the common markers routinely used in genetic diagnosis of hemophilia and which were also negative for intron 1 and 22 inversions were analyzed. Three were found to be informative exclusively with this marker (23%).


CONCLUSIONS
Hence it is a highly useful marker in the genetic diagnosis of hemophilia A families in India.
Mukundan
Preethi
P
National Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai, India.
Shetty
Shrimati
S
Kulkarni
Bipin
B
Ghosh
Kanjaksha
K
D000483:Alleles; D005091:Exons; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007194:India; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D044469:Racial Groups / Q000235:genetics
D005819:Genetic Markers; D005169:Factor VIII