Open AccessMutations in Intron 1 and Intron 22 Inversion Negative Haemophilia A Patients from Western India
Author(s) -
Preethi S. Nair,
Shrimati Shetty,
Chandrakala Shanmukhaiah,
Kanjaksha Ghosh
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0097337
Subject(s) - haemophilia a , missense mutation , medicine , genotype , intron , nonsense mutation , gastroenterology , haemophilia , mutation , genetics , gene , biology
Despite increased awareness and diagnostic facilities, 70–80% of the haemophilia A (HA) patients still remain undiagnosed in India. Very little data is available on prevalent mutations in HA from this country. We report fifty mutations in seventy one Indian HA patients, of which twenty were novel. Ten novel missense mutations [ p.Leu11Pro (p.Leu-8Pro), p.Tyr155Ser (p.Tyr136Ser), p.Ile405Thr (p.Ile386Thr), p.Gly582Val (p.Gly563Val) p.Thr696Ile (p.Thr677Ile), p.Tyr737Cys (p.Tyr718Cys), p.Pro1999Arg (p.Pro1980Arg) , p.Ser2082Thr (p.Ser2063Thr), p.Leu2197Trp (p.Leu2178Trp), p.Asp2317Glu (p.Asp2298Glu)] two nonsense [ p.Lys396* (p.Lys377* ), p.Ser2205* (p.Ser2186*) ], one insertion [ p.Glu1268_Asp1269ins (p.Glu1249_Asp1250 )] and seven deletions [ p.Leu882del (p.Leu863del), p.Met701del (p.Met682del ), p.Leu1223del (p.Leu1204del), p.Trp1961_Tyr1962del (p.Trp1942_Tyr1943del) p.Glu1988del (p.Glu1969del), p.His1841del (p.His1822del), p.Ser2205del (p.Ser2186del) ] were identified. Double mutations ( p.Asp2317Glu; p.Thr696Ile ) were observed in a moderate HA case. Mutations [ p. Arg612Cys (p.Arg593Cys), p.Arg2326Gln (p.Arg2307Gln )] known to be predisposing to inhibitors to factor VIII (FVIII) were identified in two patients. 4.6% of the cases were found to be cross reacting material positive (CRM+ve). A wide heterogeneity in the nature of mutations was seen in the present study which has been successfully used for carrier detection and antenatal diagnosis in 10 families affected with severe to moderate HA.