PMID- 25825553
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150331
LR  - 20240322
IS  - 0971-4502 (Print)
IS  - 0974-0449 (Electronic)
IS  - 0971-4502 (Linking)
VI  - 31
IP  - 2
DP  - 2015 Jun
TI  - Violating the theory of single gene-single disorder: inhibitor development in 
      hemophilia.
PG  - 162-8
LID - 10.1007/s12288-014-0473-2 [doi]
AB  - Hemophilia is clinically and genetically heterogeneous blood disorder with 
      several known gene defects accounting for the diversity of disease phenotype and 
      inhibitor production. Although increasing number of causative mutations have been 
      reported, not much is known regarding the root cause of inhibitor development 
      against infused blood clotting factors, which represents a major challenge in the 
      treatment of disease. The variations in the severity and frequency of bleeding in 
      hemophiliacs with same molecular defect, indicates the role of modifier genes in 
      the pathogenesis of disease. Herein, we aim to review and summarise the 
      literature over the past decade, to gain insight into what is critical for the 
      development of inhibitors in hemophilia. Aside from potential mutations in factor 
      VIII and IX, polymorphisms in various genes such as human leukocyte antigen-I 
      (HLA-I), HLA-II, tumor necrosis factor-alpha, interleukin-10 and cytotoxic 
      T-lymphocyte associated antigen-4, also tends to contribute to the development of 
      inhibitors. Violating the theory of single gene-single disorder, new research 
      indicates that inhibitor arise from a complex interplay of multiple genetic, 
      immunological and environmental factors. With the revolutionary advances in whole 
      genome sequencing, we propose a detailed genome wide study to identify the 
      spectrum of genetic markers involved in the development of inhibitors for better 
      diagnostics and therapeutics.
FAU - AlFadhli, Suad
AU  - AlFadhli S
AD  - Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, 
      Kuwait University, 31470, Sulaibekhat, Kuwait.
FAU - Nizam, Rasheeba
AU  - Nizam R
AD  - Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, 
      Kuwait University, 31470, Sulaibekhat, Kuwait.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20141120
PL  - India
TA  - Indian J Hematol Blood Transfus
JT  - Indian journal of hematology & blood transfusion : an official journal of Indian 
      Society of Hematology and Blood Transfusion
JID - 9425818
PMC - PMC4375149
OTO - NOTNLM
OT  - Hemophilia
OT  - Inhibitors
OT  - Mutations
OT  - Polymorphisms
EDAT- 2015/04/01 06:00
MHDA- 2015/04/01 06:01
PMCR- 2016/06/01
CRDT- 2015/04/01 06:00
PHST- 2014/07/25 00:00 [received]
PHST- 2014/10/27 00:00 [accepted]
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2015/04/01 06:01 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 473 [pii]
AID - 10.1007/s12288-014-0473-2 [doi]
PST - ppublish
SO  - Indian J Hematol Blood Transfus. 2015 Jun;31(2):162-8. doi: 
      10.1007/s12288-014-0473-2. Epub 2014 Nov 20.