ABSTRACT
Growth and function of the thyroid and adrenal glands are maintained and controlled by thyrotropin (TSH) and adrenocorticotrophic hormone (ACTH), respectively. The action of these trophic hormones requires the presence of functional TSH and ACTH receptors. We describe a large inbred Bedouin kindred in which profound congenital hypothyroidism and hypoadrenocortisolism occurred alone or together in eight family members belonging to four nuclear families. The high serum TSH and ACTH levels in the presence of normal or hypoplastic thyroid glands and low glucocorticoid, but not mineralocorticoid concentrations, are characteristic of resistance to TSH and ACTH. Linkage analysis, using specific polymorphic markers, excluded the involvement of the ACTH receptor but not thyrotropin receptor (TSHR). A novel point mutation was identified in exon 10 of the TSHR that replaces the normal cytosine in nucleotide 2024 with a thymidine. As a result the normal arginine in codon 609 (CGA) is replaced with a stop codon (TGA). This mutation produces a truncated TSHR lacking the third intracellular and extracellular loops, the sixth and seventh transmembrane segments, and the intracytoplasmic tail. The presence of hypothyroidism did not affect the timing, severity, and manner of clinical manifestation of hypoadrenocortisolism.
Subject(s)
Congenital Hypothyroidism , Hypothyroidism/genetics , Point Mutation , Receptors, Thyrotropin/genetics , Adolescent , Base Sequence , Child , Child, Preschool , Codon, Terminator/genetics , Consanguinity , DNA Primers/genetics , Female , Glucocorticoids/deficiency , Haplotypes , Humans , Hypothyroidism/metabolism , Infant , Male , Pedigree , Phenotype , Receptors, Corticotropin/genetics , Thyroid Hormones/deficiencyABSTRACT
BACKGROUND: We have recently described the association between the IgE antibody response to Ole e I (the major antigen from olive tree pollen) and the DR7-DQ2 haplotype in a Spanish population. OBJECTIVE AND METHODS: Due to the linkage disequilibrium between DR7 and DQ2, and thus the difficult distinction between the role of these two antigens in the T-cell activation response, we decided to solve this question by two approaches: 1. The study of another ethnic group, individuals of Arabic origin, with a presumably distinct disequilibrium linkage between DR and DQ antigens. Genomic DNA typing was performed in 46 subjects (allergic and non-allergic) by Restriction Fragment Length Polymorphism (RFLP) and results showed that patients with specific IgE antibodies alpha-Ole e I, were DR7 and/or DQ2. These data show a similar restriction pattern to those previously described for Spanish patients. The phenotypic frequency of DR7 antigen is significantly greater than in the non-allergic population, with a corrected P (Pc) value of 0.03. 2. The analysis of the genetic requirements of Ole e I response, using T-cell lines specific for this antigen. This was first carried out by blocking the proliferative response of these T-cell lines with specific anti-human HLA class II antibodies and then testing the genetic restriction of this response using a panel of histocompatible and histoincompatible Antigen Presenting Cells (APCs). Both experiments corroborate the hypothesis that DR7 and DQ2 are implicated in the recognition of Ole e I.
Subject(s)
HLA-DQ Antigens/immunology , HLA-DR7 Antigen/immunology , Hypersensitivity/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Arabs , Cells, Cultured , Child , Child, Preschool , HLA-DQ Antigens/genetics , HLA-DR7 Antigen/genetics , Humans , Hypersensitivity/ethnology , Immunoglobulin E/immunology , Infant , Infant, Newborn , Middle Aged , Pollen/immunology , Polymorphism, Restriction Fragment LengthABSTRACT
Sensitivity to olive pollen was studied (by skin tests) in different Israeli populations suffering from respiratory allergies. The results were compared with aerobiological data, in order to correlate amount of exposure to prevalence of sensitization. It was found that in the Jewish population, sensitivity to olive pollen developed in direct proportion with the number of olive trees in the settlement: 66% where trees density is high, 29% where it is low. In the Arab population however, possibly genetically determined, the sensitization to olive pollen was low (only 14%) even though the density of trees is high.
Subject(s)
Allergens/adverse effects , Ethnicity , Jews , Pollen , Rhinitis, Allergic, Seasonal/ethnology , Ethnicity/genetics , Humans , Hypersensitivity, Immediate/ethnology , Hypersensitivity, Immediate/genetics , Israel/epidemiology , Jews/genetics , Rhinitis, Allergic, Seasonal/etiology , Rhinitis, Allergic, Seasonal/genetics , TreesABSTRACT
Two children with typical clinical and haematological features of monosomy 7 myeloproliferative syndrome are presented. Both children displayed decreased production of beta-globin chains and unbalanced high alpha/non-alpha synthetic ratios similar to those characteristic of homozygous beta-thalassaemia. These provide further evidence for the involvement of the erythroid line as part of the malignant clone, indicating neoplastic transformation of a pluripotential stem cell in this disease.
