Analysis of factor VIII gene intron 1 inversion in Argentinian families with severe haemophilia A and a review of the literature

Rossetti, Liliana Carmen; Candela, M.; Bianco, Ra??l P??rez; Pinto, Miguel; Western, Andrea; Goodeve, Anne; Larripa, Irene; Brasi, Carlos Daniel de

doi:10.1097/00001721-200409000-00006

Cited by 13 publications

(15 citation statements)

References 12 publications

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“…There were 5.2% (6 of 115) patients with intron 1 inversion in our study and 3.3% (3 of 91) unrelated families had this mutation, which is slightly higher than the 0.7–2.7% reported in the literature (Table 1). Furthermore, 7.6% of 79 severe HA patients in our study were found to have this inversion, which is apparently higher than the 2–5% reported in the literature [3,7,31]. Aside from the high frequency of intron 22 and 1 inversions, HA is caused by a large variety of less frequent mutations scattered throughout the 26 exons of FVIII gene.…”

Section: Discussioncontrasting

confidence: 55%

Genetic analysis of haemophilia A in Taiwan

Chen

Cheng

et al. 2010

Haemophilia

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Haemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene. Identification of these mutations is becoming increasingly important in a variety of clinical settings. The purpose of this report is to describe our experience of FVIII gene mutation analysis in the largest cohort of patients in Taiwan including the discovery of 21 novel mutations. We tested 115 HA patients from 91 unrelated families, including 79 severe, 15 moderate and 21 mild types starting with an assay for the intron 22 inversion by long range-PCR followed if necessary by additional genetic studies. Intron 22 inversion accounted for 27.8% of the total and 36.7% of severe HA patients respectively while intron 1 inversion comprised 7.6% of severe patients. These were clearly different from the known data in caucasian populations. Of 75 patients without intron 22 or 1 inversion, 70 from 62 unrelated families revealed 56 different mutations by denaturing high-performance liquid chromatography (DHPLC), of which 21 were novel. Also, the only female patient with severe HA was found to have heterozygous non-sense mutation (c.6683G>A) of exon 24. Seven patients, including five without amplified PCR product and two without encoded DNA defect turned out to have exon(s) deletion or insertion by reverse transcript PCR (RT-PCR). In our study, the combination of various molecular techniques including LR-PCR, multiplex PCR, DHPLC and RT-PCR analysis enabled definitive detection of the causative FVIII gene defects in 112 of 113 (99%) HA patients.

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Section: Discussioncontrasting

confidence: 55%

Genetic analysis of haemophilia A in Taiwan

Chen

Cheng

et al. 2010

Haemophilia

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“…Our findings confirm those of previous studies. The frequency of Inv 22 in our study was 44 %, which is similar to that in populations studied in the United Kingdom [13], Spain [17], Italy [18], Argentina [19,20], India [21], Egypt [22], Iran [23], Mexico [24], Hungary [15], and Costa Rica [25]. On the basis of these results, we concluded that the incidence in different populations is similar.…”

Section: Discussionsupporting

confidence: 86%

Genotyping of Intron Inversions and Point Mutations in Exon 14 of the FVIII Gene in Iranian Azeri Turkish Families with Hemophilia A

Khaniani

Ebrahimi

Daraei

et al. 2016

Indian J Hematol Blood Transfus

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Hemophilia A (HA) is an inherited X-linked bleeding disorder caused by a variety of mutations that are distributed throughout the large FVIII gene (F8). The most common mutations in studied populations with severe HA are introns 22 and 1 inversions, gross exon deletions and point mutations in exon 14. The aim of this study was to define the frequency of these common mutations in Iranian population of Azeri Turkish in North West of Iran. Fifty patients with severe HA and forty-three female potential carriers were genotyped by inverse shifting polymerase chain reaction (IS-PCR), long-range PCR, multiplex PCR, and sequencing methods for the detection of Intron 22 and 1 inversions, gross exon deletions, and exon 14 point mutations, respectively. F8 intron 22 inversion was detected in 22 (44 %) out of 50 patients. Moreover, we detected one intron 1 inversion (2 %), and one point mutation in exon 14 (2 %). In this population, 52 % of the patients with hemophilia A did not show to carry a mutation in the analyzed regions by three mentioned methods. F8 intron 22 inversion was the major causative mutation in nearly 50 % of severe HA cases in an Azerbaijani Turkish population, which is similar to the incidence of other populations. IS-PCR is a robust, rapid, efficient, and costeffective method for the genetic analysis of patients with severe HA and for HA carrier detection, especially in developing countries.

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“…Using Southern blotting, molecular diagnosis of Inv22 has been available in Argentina since 1995. Shortly after the second recurrent inversion affecting F8 , intron 1 (Inv1), was described, our series was reported along with a review of the literature estimating that Inv1 causes <3% of severe‐HA in Argentina . Inv22 originates from homologous recombination between a 9.5 kb sequence located within F8 intron 22 ( int22h ‐1) and one of two oppositely oriented extragenic copies of int22h ( int22h ‐2 and int22h ‐3) located by the Xq‐telomere.…”

Section: Haemophilia Genetic Analysis – the Argentinian Experience: Dmentioning

confidence: 98%

Genetic testing in bleeding disorders

et al. 2014

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Summary The aim of molecular genetic analysis in families with haemophilia is to identify the causative mutation in an affected male as this provides valuable information for the patient and his relatives. For the patient, mutation identification may highlight inhibitor development risk or discrepancy between different factor VIII assays. For female relatives, knowledge of the familial mutation can facilitate carrier status determination and prenatal diagnosis. Recent advances in understanding mutations responsible for haemophilia and methods for their detection are presented. For reporting of such mutations, participation in external quality assessment ensures that essential patient and mutation details are routinely included and that pertinent information is incorporated in the interpretation.

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Analysis of factor VIII gene intron 1 inversion in Argentinian families with severe haemophilia A and a review of the literature

Cited by 13 publications

References 12 publications

Genetic analysis of haemophilia A in Taiwan

Genetic analysis of haemophilia A in Taiwan

Genotyping of Intron Inversions and Point Mutations in Exon 14 of the FVIII Gene in Iranian Azeri Turkish Families with Hemophilia A

Genetic testing in bleeding disorders

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