Use of Intron 1 and 22 inversions and linkage analysis in carrier detection of hemophilia A in Indians.
BACKGROUND
Hemophilia A is an X-linked recessively inherited bleeding disorder characterized by deficiency of procoagulant factor VIII (FVIII).


METHODS
Sixty unrelated hemophilia A patients and their family members have undergone tests for carrier detection by linkage analysis using the polymorphic markers Bcl I, Xba I and Intron 13 or 22 VNTRs. In families of sporadic hemophiliacs, the carrier status of female subjects was ascertained by linkage analysis along with FVIII:C/VWD Ag estimation.


RESULTS
Of the 33 families with positive family history, the defective X chromosome was tracked in 28 mothers. The carrier status of females from hemophilia A families with positive family history, ascertained by linkage analysis and Intron 22 and 1 inversion, was made out in 85% cases. FVIII:C/VWF Ag ratio was evaluated in 36 females from 9 sporadic hemophilic families. Using the FVIII:C/VWF Ag ratio along with linkage analysis, carrier status was determined in 9 (25%) of the 36 females studied. Using Intron 22 inversion along with linkage analysis and FVIII:C/VWF Ag estimation, the informativity in female subjects from families of sporadic hemophiliacs increased from 25% to 52%.


CONCLUSIONS
In the West, linkage analysis with Bcl I, Xba I and Intron 13 or 22 VNTR markers and inversion 22 offers a good tool for carrier detection of hemophilia A in India.
Ahmed
Rafeeq
R
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India.
Kannan
Meganathan
M
Biswas
Arijit
A
Ranjan
Ravi
R
Choudhry
Ved P
VP
Saxena
Renu
R
D007446:Chromosome Inversion; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007194:India; D007438:Introns; D008297:Male; D009154:Mutation