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ABSTRACT: A previously undescribed mutation (-1, +3, codon 24) causing beta-thalassaemia was identified in an Egyptian patient. It consists in the concomitant deletion of a G in codon 24 and its replacement with the new trinucleotide CAC, thus resulting in the shift of the beta-globin reading frame. The sequence of the chromosome of interest was isolated from the homologous one by means of selective hybridization to an immobilized oligonucleotide. The presence of this mutation in the proband's family was confirmed by dot blot hybridization with an oligonucleotide probe.
British Journal of Haematology 10/1991; 79(1):90-2. · 4.94 Impact Factor
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ABSTRACT: Fifteen sibships, each having two or more siblings affected by classical or definite RA were studied. They comprised 31 patients with RA (all in remission) and 21 normal siblings. The total severity index of RA was assessed by clinical and radiological indices. For all the patients the following investigations were carried out: (1) HLA antigens determination for nine antigens at A locus and 15 at B locus and 6 at DR locus; (2) rheumatoid factor. We found: (1) RA disease is genetically controlled and the responsible genes are linked to the HLA system; (2) association between seropositivity and DR4 and DR4/B27 genotypes; (3) significant effect of the genotype DR4/B27 on the age of onset; (4) association between the increase in disease severity both clinical and radiological and DR4/X and DR4/B27 phenotypes. Thus the genetic control is probably composed of two types of genes: disease susceptibility genes and disease severity genes linked to DR4/X and DR4/B27 phenotypes.
British journal of rheumatology 07/1991; 30(3):181-5.
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ABSTRACT: The relative frequency of different beta-thalassemia mutations and their association with beta-globin haplotypes were studied in patients from the Nile delta region, Egypt, by means of the polymerase chain reaction, oligonucleotide hybridization and restriction analysis. We found that 8 mutations account for 77% of beta-thalassemia chromosomes in this population, the commonest being IVS-1 nt 110, IVS-1 nt 6 and IVS-1 nt 1. Each mutation was associated with a specific haplotype, with the exception of IVS-1 nt 110, found on 3 different chromosomal backgrounds. Our data show that testing for the 8 detectable mutations makes feasible prenatal diagnosis in 65% of at risk couples and exclusion testing in an additional 25% of cases.
Human Genetics 09/1990; 85(3):272-4. · 5.07 Impact Factor
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A. Novelletto,
M. Hafez,
G. Deidda,
A. Rienzo,
L. Felicetti,
H. El-Tahan,
Z. Morsi, M. El-Ziny,
Y. Al-Tonbary,
A. Sittien,
L. Terrenato
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ABSTRACT: The relative frequency of different -thalassemia mutations and their association with -globin haplotypes were studied in patients from the Nile delta region, Egypt, by means of the polymerase chain reaction, oligonucleotide hybridization and restriction analysis. We found that 8 mutations account for 77% of -thalassemia chromosomes in this population, the commonest being IVS-1 nt 110, IVS-1 nt 6 and IVS-1 nt 1. Each mutation was associated with a specific haplotype, with the exception of IVS-1 nt 110, found on 3 different chromosomal backgrounds. Our data show that testing for the 8 detectable mutations makes feasible prenatal diagnosis in 65% of at risk couples and exclusion testing in an additional 25% of cases.
Human Genetics 07/1990; 85(3):272-274. · 5.07 Impact Factor
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ABSTRACT: The study included the members of 15 families, each having more than one sibling affected by rheumatic fever (RF). All the rheumatic individuals showed the sequelae of rheumatic carditis, but on clinical and laboratory evidence, the disease was inactive. Thirty normal unrelated individuals, having no rheumatic first-degree relatives, were studied as controls. The following investigations were carried out for all members: (1) history and clinical examination, (2) routine investigations of diagnosis, (3) HLA typing using 9-A, 15-B, 6-DR antigens, (4) adherence of group A streptococci to pharyngeal cells, an in vitro adherence assay. There were two types of strains; five RF-associated strains and two RF-unassociated strains. Statistical and genetic analysis revealed: (1) no significant difference between adherence of RF-associated and unassociated strains amongst controls; (2) significant increased avidity for adherence of RF-associated strains amongst rheumatic siblings compared to normal siblings and controls. There was no significant difference between the three groups using RF-unassociated strains; (3) HLA-haplotype concordance and 'N' measure showed that the avidity for adherence is probably inherited; (4) lod scores for linkage suggest a dominant susceptibility gene(s) closely linked to HLA and segregating in multiplex families.
British journal of rheumatology 09/1989; 28(4):304-9.
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ABSTRACT: The frequency of deletional alpha-thalassemia in the Egyptian population was estimated at 0.08 by DNA analysis of a newborn random sample. No alpha 0 determinants were found. The most frequent alpha+ determinant was the -alpha 3.7 type I in association with the medium allele at inter-zeta HVR. The -alpha 4.2 and alpha alpha alpha anti 3.7 arrangements were found at very low frequencies.
Human Genetics 03/1989; 81(3):211-3. · 5.07 Impact Factor
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ABSTRACT: The study included three groups of children: (a) 38 with active rheumatic fever (ARF) and active carditis; 21 seen during their first attack and 17 during recurrence of activity, (b) 47 with inactive rheumatic fever (IARF); the period since activity was less than 3 years in 31 cases and more than 3 years in 16 cases. Using monoclonal antibodies and T lymphocyte blast transformation induced by PHA, we found: (1) low total T lymphocytes, helper-inducer cells and helper-inducer/suppressor-cytotoxic ratio which persisted for years; and (2) reduced lymphoblast transformation in active disease.
British journal of rheumatology 07/1988; 27(3):181-6.
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ABSTRACT: In a study of rheumatic carditis, 135 members of 21 multiplex families have been investigated, along with 60 normal unrelated control individuals. Circulating T-lymphocytes were reduced (as a percentage of total blood mononuclear cells) in all 'rheumatic' individuals, in 7 of 40 normal parents, and in 8 of 49 normal sibs. An immune response characterized by an increase in the proportion of suppressor T cells occurs in most individuals affected by rheumatic carditis and this change persists for a long time. Genetic analysis revealed three important points: 1. increased HLA haplotype sharing amongst the affected sib-pairs; 2. the possibility of using low circulating T-cell percentage as a marker of susceptibility; 3. presumptive evidence for a recessive susceptibility gene linked to HLA and responsible for the suppressor cell response.
Disease markers 10/1987; 5(3):177-85. · 1.64 Impact Factor
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ABSTRACT: Thirty-nine mentally normal unrelated children diagnosed as having febrile convulsions were included in this study. The following have been carried out: (a) detailed anamnesis and clinical examination; (b) cerebrospinal fluid investigation; (c) EEG examination between attacks; (d) HLA-antigen determination; (e) estimation of serum IgA, IgG, IgM; and (f) counting of percent spontaneous E-rosette formation. The results were statistically compared to normal Egyptian controls. The results could be summarised as follows. (1) Only HLA-B5 antigen frequency is high among patients (chi 2c = 19.1, P less than 0.0001). Relative risk is 4.4 which shows significant association (WY2 = 29.145, P less than 0.0001) and etiologic fraction equals 0.377. (2) The means of IgA and E-rosette in the patients were significantly low (t = 3.46, P less than 0.01 and t = 3.92, P less than 0.001, respectively), (3) HLA-B5 is the only antigen with high frequency among the two groups of patients with low IgA and E-rosette (chi 2c = 11.9 and 18.2, respectively). (4) There is a significant association between B5 and low IgA (P less than 0.05) but not with low E-rosette (P greater than 0.05). The suggestion is that the genetic control of febrile convulsions is in linkage disequilibrium with HLA-B5, low IgA and low total T-cells. This altered immune function in otherwise normal children with febrile convulsions may predispose them to acute infections and high fever which precipitate convulsions.
Journal of Neurogenetics 09/1987; 4(5):267-74. · 2.42 Impact Factor
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ABSTRACT: The study included 16 infants with advanced manifestations of kwashiorkor and 16 unrelated age-matched normals as controls. Whole blood samples, at room temperature, were exposed to gamma-rays in increasing dosages. Lymphocytes were cultured; phytohaemagglutinin and bromodeoxyuridine (10 microM) were added, at initiation of culture, and harvesting was performed after 64 to 68 h. Slides were coded and sister chromatid exchanges (SCE) counted. In controls, no significant increase in the frequency of SCE was found. For kwashiorkor infants the SCE frequencies showed significant increase as irradiation dosages rose. It is concluded that the changes observed are probably due to alteration in: the cell cycle length; activities of enzymes responsible for DNA repair; DNA growing points; and protection of cells from chromosome breakage.
The Journal of tropical medicine and hygiene 09/1987; 90(4):171-5.
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ABSTRACT: Thirteen multicase Egyptian families (having more than one sib affected) with pulmonary tuberculosis have been studied. They include 26 parents (4 were tuberculous) and 53 sibs (30 tuberculous and 23 healthy). For all of them the following have been carried out: (a) Clinical, radiological, and bacteriological examination for diagnosis and evaluation of the disease severity; HLA-antigen determination using 9(A), 16(B) and 6(DR) antigens. The analysis of data revealed: (1) high incidence of tuberculosis among sibs in families having A2 B5 in their haplotypes compared to those having A2 X or B5 X--affected sibs with A2 B5 showed more severe manifestations than those having only one of the two antigens; (2) aggregation of HLA concordance among the sib pairs, both fully identical and haploidentical, while none of the sib pairs is non-identical; (3) Lod score studies showed linkage between the genetic control of susceptibility to pulmonary tuberculosis and HLA; (4) identity by descent study confirms the dominant pattern of transmission. The recommendation is that in a clinical setting of genetic counselling healthy individuals having either A2 or B5 antigens in their haplotypes should be vaccinated with BCG. Furthermore tuberculous patients having these HLA antigens should be managed aggressively, especially those having A2 B5 haplotypes in whom the disease is likely to run a severe course.
Disease markers 10(3):143-9. · 1.64 Impact Factor
