[Aneurism of the subclavian artery associated with Turner's syndrome]. / Anévrisme sous-clavier associé à un syndrome de Turner.

UNLABELLED: Arterial aneurysms associated with Turner's syndrome are rare. CASE REPORT: We report a case of aneurysm of the left subclavian artery in a 16-year-old girl with Turner's syndrome. This patient was operated on: resection of the aneurysm, suture of the aortic arch and reimplantation of the subclavian artery in the left common carotid were performed. At 3-year follow-up, the evolution is favourable. COMMENTS: Cardiovascular anomalies are observed in 50% of subjects with Turner's syndrome. This justifies complementary cardiac investigations in these patients. Congenital malformations (bicuspid aortic valve, aortic coarctation, intracardiac communications, valvular lesions) or acquired anomalies (arterial hypertension, aortic dissection) are frequent. Only one similar case of subclavian artery aneurysm has been reported until now. The risk of rupture justifies the surgical treatment.

Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency.

The hereditary syndrome of unresponsiveness to ACTH is a rare autosomal recessive disorder characterized by low levels of serum cortisol and high levels of plasma ACTH. There is no cortisol response to exogenous ACTH. Recent cloning of the human ACTH receptor gene has enabled us to study this gene in patients with glucocorticoid deficiency. By using the PCR to amplify the coding sequence of the ACTH receptor gene, we identified three mutations in two unrelated patients. One mutation present in homozygous form converted the negatively charged Asp107, located in the third transmembrane domain, to an uncharged Asn residue. The second patient was a compound heterozygote: the paternal allele contained a one-nucleotide insertion leading to a stop codon within the third extracellular loop, and the maternal allele contained a point mutation converting Cys251 to Phe, also in the third extracellular loop. Normal and mutant ACTH receptor genes were expressed in the M3 cell line, and intracellular cAMP production in response to ACTH was measured. For the mutant receptors, no response to physiological ACTH concentrations was detected, suggesting an impaired binding of ACTH to the receptors and/or an altered coupling to the adenylate cyclase effector.

[Mutations of ACTH receptor gene and familial syndrome of glucocorticoid deficiency]. / Mutations du gène du récepteur à l'ACTH et syndrome familial de déficit en glucocorticoïdes.

Familial isolated glucocorticoid deficiency syndrome is characterized by low cortisol plasma levels despite high ACTH levels without any stimulation of steroid production after ACTH administration. However, the mineralocorticoid function is well-preserved in this syndrome which indicates a specific resistance to ACTH. Recent cloning of the ACTH receptor allowed to study this receptor in this particular syndrome. After studying sixteen affected families, we have found three mutations in two patients from non-related families. One of these patients was a double heterozygote compound (C251F, G217fs) while the other one was homozygote for another mutation D107N. The mutant receptors were expressed in vitro in transfected M3 cells (S91 Cloudman cells) which represents a working expression system to express the ACTH receptor. Production of intracellular cyclic AMP was calculated in the presence of increasing concentrations of ACTH. The EC50 values were estimated (C251F: 3.5 +/- 0.9 x 10(-9) M, D107N: 3.0 +/- 0.9 x 10(-9) M, G217fs: 4.8 +/- 0.9 x 10(-9) M) and comparison with the value obtained for the wild type ACTH receptor (5.1 +/- 0.9 x 10(-10) M) indicates a clear 6 to 9 shift to the right due to an impaired function of these mutant receptors. Such results were expected for the G217fs mutation, and could be explained by a decrease in ligand affinity or an impaired coupling to adenylate cyclase in the case of amino acid substitutions. A total of twelve mutations has been described in the literature although eight of them have not been tested in vitro until now.

A novel genetic thrombocytopenia (Paris-Trousseau) associated with platelet inclusions, dysmegakaryopoiesis and chromosome deletion AT 11q23.

We report a novel case of hereditary thrombocytopenia. A chronic thrombocytopenia was noted in a woman with mild hemorrhagic complications as well as in her very young son. A platelet fraction contained giant granules stained in red on blood smears. The number of bone marrow megakaryocytes was increased with many micromegakaryocytes. Since the platelet life span was normal, these results indicated an ineffective platelet production. A constitutional cytogenetic abnormality was detected in the two patients: a deletion of the long arm of chromosome 11. The association of these abnormalities constitute a new disorder: this never described cytological entity is a valuable model for exploring the role of some genes involved in the regulation of thrombopoiesis.