Intron 22 Inversions in Factor VIII Gene in Indian Hemophiliacs

Shetty, Shrimati; Pathare, Anil; Ghosh, Kanjaksha; Jijina, Farah; Mohanty, Dipika

doi:10.1055/s-0037-1615084

Cited by 19 publications

(12 citation statements)

References 2 publications

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“…Recently, an intron 1 inversion was also reported to be a recurrent mutation, occurring in 5% of patients with severe hemophilia A (Bagnall et al, 2002). Studies from the west have reported a prevalence of intron 22 inversion ranging from 30 to 50% in severe hemophilia A (Enayat et al, 1995;Naylor et al, 1995), which is in accordance with that found in India (Shetty et al, 1998;Jayandharan at al., 2004;Pandey et al, 2002;Ghosh et al, 2004). Shetty et al (1998) have reported a prevalence of 1.24% of intron 1 inversion positive cases (3 out of a large cohort of 241) in Mumbai population, whereas worldwide incidences record 1 to 5% Acquila et al, 2003;Rosseti et al, 2004).…”

Section: Inversionsupporting

confidence: 82%

Factor VIII genetic mutations and protein alterations in hemophilia A: A review

Faridi¹,

Kumar²,

Husain³

et al. 2014

Clin. Rev. Opinions

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Section: Inversionsupporting

confidence: 82%

Factor VIII genetic mutations and protein alterations in hemophilia A: A review

Faridi¹,

Kumar²,

Husain³

et al. 2014

Clin. Rev. Opinions

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“…Fifty consecutive patients with severe haemophilia A (FVIII < 1%) were also evaluated for inversion of intron 22 using Southern blotting and the first 25 of these patients have been described elsewhere [10]. Inhibitors in these patients were also evaluated.…”

Section: Methodsmentioning

confidence: 99%

Development of inhibitors in patients with haemophilia from India

et al. 2001

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Four hundred and seven patients (352 haemophilia A and 55 haemophilia B) were investigated for the presence of factor VIII and IX inhibitors. Twenty-four out of 292 severe and two out of 36 moderate haemophilia A patients showed the presence of inhibitors. The mean age at development of inhibitors was 17.7 years (range 6-52 years). In 12 patients the inhibitors were detected due to suboptimal response to factor replacement therapy (symptomatic) and in the remaining 14 patients the inhibitors were detected during the routine screening of the patients' samples for inhibitors. They had, however, responded well to the usual doses of factor concentrates and there was no suspicion in these patients that they had developed an inhibitor (asymptomatic). There were two families in which the inhibitors were detected in more than one family member. The level of inhibitors in symptomatic patients ranged from 2.2 Bethesda units (BU) mL(-1) to 460.6 BU mL(-1), and in asymptomatic patients it ranged from 0.8 BU mL(-1) to 3.2 BU mL(-1). The inhibitors persisted in all patients except one, who developed an inhibitor postoperatively for a brief period of 3 months. All these patients were followed up from first factor exposure and were tested for inhibitors at least twice a year. The mean number of exposure days before they developed inhibitors was 47.5 exposure days (range 17-98 exposure days). No inhibitors appeared after more than 100 exposure days in any of the patients. When 50 consecutive patients were investigated for intron 22 inversions of the factor VIII gene, 17 patients were found to be positive for inversions (10 proximal inversion; seven distal inversion) out of whom four patients developed inhibitors, three patients belonging to the same family. Out of 35 haemophilia B patients, only one patient developed an inhibitor. The overall prevalence of inhibitors was thus 8.2%, which is similar to the reports from western countries, prior to the introduction of highly purified factor concentrate therapy.

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“…R1689 or R2209Q [10]. The intron 22 inversion of the FVIII gene, the only one we studied, was absent in all 11 cases, in contrast to the 25% prevalence in our severe haemophiliacs [15]. Therefore, no conclusion can be drawn regarding this, nor regarding the quantitative analysis of the factor V Leiden mutation at the protein level, as APC resistance by clotting assay was not estimated in our study.…”

Section: Discussionmentioning

confidence: 78%

Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one‐stage assay

2001

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During the course of investigations we encountered 11 patients with haemophilia A who had severe factor VIII deficiency as measured by one‐stage assay but had surprisingly mild clinical presentation. Four of these patients had either a brother, nephew or maternal uncle with severe clinical manifestations. Two patients had low protein S levels, and one was heterozygous for the factor V Leiden mutation. One patient had a combined deficiency of protein C and antithrombin III. Four patients had a two‐stage factor VIII assay value that was much higher than the one‐stage assay value. Five patients were heterozygous for the MTHFR gene C677T polymorphism, of whom two patients were also deficient for protein S and one had two‐stage factor assay values higher than the one‐stage assay values. The patient who was both factor VIII deficient and heterozygous for factor V Leiden had mild clinical presentation as compared to his maternal uncle who was only factor‐VIII deficient. The maternal cousin of the same patient was heterozygous for factor V Leiden and had suffered two thrombotic episodes. Thus, the present study advocates that the physiological inhibitors of blood coagulation also play an important role in cases of haemophilia A in the final outcome of haemostasis in vivo.

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Intron 22 Inversions in Factor VIII Gene in Indian Hemophiliacs

Cited by 19 publications

References 2 publications

Factor VIII genetic mutations and protein alterations in hemophilia A: A review

Factor VIII genetic mutations and protein alterations in hemophilia A: A review

Development of inhibitors in patients with haemophilia from India

Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one‐stage assay

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