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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

Segregation analysis of the CD18 specific markers Xba1 and Ava II with the mutations causing leukocyte adhesion deficiency in four Tunisian families. Family trees were drawn using the Pedraw software. Individuals within each nuclear family are numbered using Arabic numbers. The double bars indicate consanguineous mating. ND = not determined.
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Figure 4: Segregation analysis of the CD18 specific markers Xba1 and Ava II with the mutations causing leukocyte adhesion deficiency in four Tunisian families. Family trees were drawn using the Pedraw software. Individuals within each nuclear family are numbered using Arabic numbers. The double bars indicate consanguineous mating. ND = not determined.

Mentions: Segregation of two CD18 intragenic polymorphic markers Ava II and Xba1 with the mutations underlying LAD in our patients was studied using site tagged sequence analysis (STS). The Ava II polymorphism was studied by an STS assay described elsewhere [13]. Familial studies have shown (see Figure 4) that the 1497delG mutation, present in all the patients, segregates with the (Ava II+, Xba I+) markers. This strong linkage desequilibrium was confirmed by the study of the patients close relatives; Chi square = 41.5, p = 0.001 as calculated using the Four Fold Table method described by Feiss [18]. This allelic association was present in all the chromosomes exhibiting the 1497delG mutation and in 18 out of the 54 chromosomes studied. Interestingly, the allele frequency of the Ava II marker in the non-affected Tunisian population was identical to the one reported in the Japanese population [13] (i.e., 0.7 for the Ava II+ allele and 0.3 for the Ava II-allele).


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)

Segregation analysis of the CD18 specific markers Xba1 and Ava II with the mutations causing leukocyte adhesion deficiency in four Tunisian families. Family trees were drawn using the Pedraw software. Individuals within each nuclear family are numbered using Arabic numbers. The double bars indicate consanguineous mating. ND = not determined.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Segregation analysis of the CD18 specific markers Xba1 and Ava II with the mutations causing leukocyte adhesion deficiency in four Tunisian families. Family trees were drawn using the Pedraw software. Individuals within each nuclear family are numbered using Arabic numbers. The double bars indicate consanguineous mating. ND = not determined.
Mentions: Segregation of two CD18 intragenic polymorphic markers Ava II and Xba1 with the mutations underlying LAD in our patients was studied using site tagged sequence analysis (STS). The Ava II polymorphism was studied by an STS assay described elsewhere [13]. Familial studies have shown (see Figure 4) that the 1497delG mutation, present in all the patients, segregates with the (Ava II+, Xba I+) markers. This strong linkage desequilibrium was confirmed by the study of the patients close relatives; Chi square = 41.5, p = 0.001 as calculated using the Four Fold Table method described by Feiss [18]. This allelic association was present in all the chromosomes exhibiting the 1497delG mutation and in 18 out of the 54 chromosomes studied. Interestingly, the allele frequency of the Ava II marker in the non-affected Tunisian population was identical to the one reported in the Japanese population [13] (i.e., 0.7 for the Ava II+ allele and 0.3 for the Ava II-allele).

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