Importance of investigating somatic and germline mutations in hemophilia A: a preliminary study from All India Institute of Medical Sciences, India.
BACKGROUND
Hemophilia A is a common hereditary bleeding disorder caused mainly by mutations in the Factor VIII (FVIII) gene, which results in defective or absent FVIII protein. Most of the causative mutations arise from the germ cells, which leads to either heterozygous or hemizygous state for the mutation in the next generation. Germline or somatic mosaic may result due to a de novo mutation during early embryogenesis.


METHODS
We analyzed 14 families of Indian origin with Hemophilia A [sporadic and severe] for the presence of mosaic individuals by employing Allele Specific PCR, mutation enrichment experiment and sequencing.


RESULTS
Nine families had point mutations, 3 families had small deletions or insertions, 2 families had splice site mutations. The origin of the de novo mutation was assigned to the patients' mother in 8 families. For 4 families it was assigned to the maternal grandmother and to the maternal grandfather in 2 families. In a single family somatic mosaic was detected.


CONCLUSIONS
The presence of somatic mosaic in families with sporadic Hemophilia A in India may confound risk estimation during genetic counseling.
Ranjan
Ravi
R
Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
Biswas
Arijit
A
Meena
Arvind
A
Akhter
Mohammad Suhail
MS
Yadav
Birendra Kumar
BK
Ahmed
Rafeeq Habeeb
RH
Saxena
Renu
R
D001483:Base Sequence; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007194:India; D009030:Mosaicism; D009154:Mutation
D017931:DNA Primers