Are int22h-mediated deletions a common cause of hemophilia?

MIGUEL MARTÍN ABELLEYRO; LILIANA CARMEN ROSSETTI; CLAUDIA PAMELA RADIC; MIGUEL CANDELA; IRENE B. LARRIPA; CARLOS D. DE BRASI

ANNALS OF HEMATOLOGY

SPRINGER

Lugar: Berlin; Año: 2012 vol. 91 p. 633 - 636

0939-5555

The first objective is to present our Argentinean series of 79 patients with severe Hemophilia A screened for int22h-mediated rearrangements and we found the classical intron 22 inversions with patterns type I and type II, and the absence of Del22 (int22h-mediated deletions). Our findings represent the typical results obtained from international series of severely affected HA patients, in contrast with the three (out of 13) Egyptian patients with the Del22 found by Abou-Elew et al (2011). These latter three cases described in Egyptian patients with HA are extremely interesting, but as its molecular diagnosis has been only relied on inverse shifting-PCR (Rossetti et al, 2008), which with Southern blot analysis described by Lakich et al, 1993; and long distance-PCR designed by Bagnall et al, 2006; is one of the practical approaches for genotyping all int22h-mediated rearrangements (including Del22 type I and II), thus far. In this scenario and the previous believe that Del22 would be extremely deleterious in hemizygous males (even to the point to compromise viability), we suggest that Del22 molecular diagnosis needs further support by use of other (non-related) genotyping approaches. In this Letter to Editor we provide to the scientific community (and Abou-Elew et al, in particular), with a simple practical approach to further support Del22 molecular diagnosis in addition to those available for genotyping all int22h-mediated rearrangements. Consequently, the second objective of this paper is to present a bioinformatics work on a theoretically defined Del22 gap interval (NC_000023.10:g.154118607_154615713del) and its potential consequences on the patient?s genotype and phenotype associated with the loss of well defined DNA markers (particularly STS), and gene functions, respectively. To improve clarity of the paper, and taking into account that the subject is extremely interesting but extremely complex at same time, we ask you for permission to exceed the word count (1200) and number of references (14) allowed for a Letter to Editor in Annals of Hematology.