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Two Novel Frame Shift, Recurrent and De Novo Mutations in the ITGB2 (CD18) Gene Causing Leukocyte Adhesion Deficiency in a Highly Inbred North African Population.

Fathallah DM, Jamal T, Barbouche MR, Bejaoui M, Hariz MB, Dellagi K - J. Biomed. Biotechnol. (2001)

Bottom Line: We have also characterized a novel Xba1 polymorphic site located at the 5' end of the ITGB2 locus.Family studies showed that the 1497delG mutation segregated with this marker and the intragenic AvaII polymorphic marker, suggesting the presence of a founder effect.In view of the literature published on the molecular genetics of LAD and considering the ethnic origin of the patients studied, our findings confirm the heterogeneity of the mutations causing LAD and point out potential mutational hot spots in the ITGB2 gene.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
We have identified four different mutations causing leukocyte adhesion Deficiency (LAD) in the ITGB2 gene of patients from a highly inbred population. Two were novel single-bp deletions (1497delG and 1920delG) causing frame shift and the two others were the missense mutations G284S and R593C. In our study, the G284S was a recurrent mutation while the R593C occurred de novo. We have also characterized a novel Xba1 polymorphic site located at the 5' end of the ITGB2 locus. Family studies showed that the 1497delG mutation segregated with this marker and the intragenic AvaII polymorphic marker, suggesting the presence of a founder effect. The observation of a heterogeneous spectrum including de novo and recurrent mutations causing LAD in a highly inbred population is rather unexpected. In view of the literature published on the molecular genetics of LAD and considering the ethnic origin of the patients studied, our findings confirm the heterogeneity of the mutations causing LAD and point out potential mutational hot spots in the ITGB2 gene.

No MeSH data available.


Related in: MedlinePlus

FACS analysis of the β2 integrin CD18 expression at thesurface of PBMCs from Tunisian patients with leukocyte adhesiondeficiency (LAD). (a) control from a non-affected individual. (b), (c) and (d) represent respectively, the CD18 expression pattern obtained in patients (I, S, R), M, and K.
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Figure 1: FACS analysis of the β2 integrin CD18 expression at thesurface of PBMCs from Tunisian patients with leukocyte adhesiondeficiency (LAD). (a) control from a non-affected individual. (b), (c) and (d) represent respectively, the CD18 expression pattern obtained in patients (I, S, R), M, and K.

Mentions: We used immunofluorescence flow cytometry to analyze the level of the CD18 subunit expression on the surface of PBMCs from five Tunisian LAD patients and their parents. As shown in Figure 1, low levels of CD18 expression (1% to 5%) were observed in the patients with the severe form of the disease. Patient K had a 16.5% CD18 expression level as compared to the normal control, which is consistent with the moderate form of LAD. All patients exhibited a normal cell surface expression of the leukocyte markers CD3, CD4, CD8, CD19, and HLA DR antigens (data not shown).


Two Novel Frame Shift, Recurrent and De Novo Mutations in the ITGB2 (CD18) Gene Causing Leukocyte Adhesion Deficiency in a Highly Inbred North African Population.

Fathallah DM, Jamal T, Barbouche MR, Bejaoui M, Hariz MB, Dellagi K - J. Biomed. Biotechnol. (2001)

FACS analysis of the β2 integrin CD18 expression at thesurface of PBMCs from Tunisian patients with leukocyte adhesiondeficiency (LAD). (a) control from a non-affected individual. (b), (c) and (d) represent respectively, the CD18 expression pattern obtained in patients (I, S, R), M, and K.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC129056&req=5

Figure 1: FACS analysis of the β2 integrin CD18 expression at thesurface of PBMCs from Tunisian patients with leukocyte adhesiondeficiency (LAD). (a) control from a non-affected individual. (b), (c) and (d) represent respectively, the CD18 expression pattern obtained in patients (I, S, R), M, and K.
Mentions: We used immunofluorescence flow cytometry to analyze the level of the CD18 subunit expression on the surface of PBMCs from five Tunisian LAD patients and their parents. As shown in Figure 1, low levels of CD18 expression (1% to 5%) were observed in the patients with the severe form of the disease. Patient K had a 16.5% CD18 expression level as compared to the normal control, which is consistent with the moderate form of LAD. All patients exhibited a normal cell surface expression of the leukocyte markers CD3, CD4, CD8, CD19, and HLA DR antigens (data not shown).

Bottom Line: We have also characterized a novel Xba1 polymorphic site located at the 5' end of the ITGB2 locus.Family studies showed that the 1497delG mutation segregated with this marker and the intragenic AvaII polymorphic marker, suggesting the presence of a founder effect.In view of the literature published on the molecular genetics of LAD and considering the ethnic origin of the patients studied, our findings confirm the heterogeneity of the mutations causing LAD and point out potential mutational hot spots in the ITGB2 gene.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
We have identified four different mutations causing leukocyte adhesion Deficiency (LAD) in the ITGB2 gene of patients from a highly inbred population. Two were novel single-bp deletions (1497delG and 1920delG) causing frame shift and the two others were the missense mutations G284S and R593C. In our study, the G284S was a recurrent mutation while the R593C occurred de novo. We have also characterized a novel Xba1 polymorphic site located at the 5' end of the ITGB2 locus. Family studies showed that the 1497delG mutation segregated with this marker and the intragenic AvaII polymorphic marker, suggesting the presence of a founder effect. The observation of a heterogeneous spectrum including de novo and recurrent mutations causing LAD in a highly inbred population is rather unexpected. In view of the literature published on the molecular genetics of LAD and considering the ethnic origin of the patients studied, our findings confirm the heterogeneity of the mutations causing LAD and point out potential mutational hot spots in the ITGB2 gene.

No MeSH data available.


Related in: MedlinePlus