Browsing by Author "Eggers, M"

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    gps Mutations in Chilean patients harboring growth hormone-secreting pituitary tumors
    (WALTER DE GRUYTER GMBH, 1999) Johnson, MC; Codner, E; Eggers, M; Mosso, L; Rodriguez, JA; Cassorla, F
    Hypersecretion of GH is usually caused by a pituitary adenoma and about 40% of these tumors exhibit missense gsp mutations in Arg(201) or Gln(227) of the Gs(alpha) gene. We studied 20 pituitary tumors obtained from patients with GH hypersecretion, One tumor was resected from an 11 year-old boy with a 3 year history of accelerated growth, associated with increased concentrations of serum GH and IGF-I, which were not suppressed by glucose administration, The remaining 19 tumors were obtained from adult acromegalic patients, who had elevated baseline serum GH levels that did not show evidence of suppression after administration of glucose, The gsp mutations were studied by enzymatic digestion of the amplified PCR fragment of exon 8 (Arg(201)) and exon 9 (Gln(227)) with the enzymes NlaIII and NgoAIV, respectively. The tumors obtained from the boy and from nine of the 19 patients with acromegaly exhibited the gsp mutation R201H. None of the tumors had the Gln(227) mutation. The gsp positive patients tended to be older, had smaller tumors, and had preoperative basal serum GH levels which were significantly lower (21 +/- 6 vs 56 +/- 16 mu g/l, p < 0.05) than the gsp negative patients, In this study, we documented the presence of a gsp mutation in Arg(201) in a boy with gigantism and in approximately half of 19 Chilean adult patients with acromegaly, similar to other populations.
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    Study of GH sensitivity in Chilean patients with idiopathic short stature
    (ENDOCRINE SOC, 2001) Sjoberg, M; Salazar, T; Espinosa, C; Dagnino, A; Avila, A; Eggers, M; Cassorla, F; Carvallo, P; Mericq, MV
    We hypothesized that some children with idiopathic short stature in Chile might bear heterozygous mutations of the GH receptor. We selected 26 patients (3 females, 23 males) from 112 patients who consulted for idiopathic short stature at the University of Chile. Their chronological age was 8.3 +/-1.9, and bone age was 6.1 +/-1.0 yr. Their height was -3.0 +/-0.7 SDS; IGF-I, -1.2 +/-1.1 SD; IGF binding protein 3, -0.7 +/-2.0 SDS; and GH binding protein, 0.4 +/-0.8 SDS. Patients were admitted, and blood samples were obtained every 20 min to determine GH concentrations overnight. Coding sequences and intron-exon boundaries of exons 2-10 of GH receptor gene were amplified by PCR and subsequently analyzed through single-strand conformational analysis. Mean serum GH concentration, over 12-h, was 0.20 +/-0.08 nm; pulse amplitude, 0.40 +/-0.15 nM; number of peaks, 5.8 +/-1.5 peaks/12 h; peak value of GH during the 12-h sampling, 1.03 +/-0.53 nm; and area under the curve, 151.4 +/- 56.1 nM/12 h. There were positive correlations between mean GH vs. area under the curve (P<0.001) and GH peak (P<0.01). The single-strand conformational analysis of the GH receptor gene showed abnormal migration for exon 6 in 9 patients and for exon 10 in 9 patients, which (by sequence analysis) corresponded to 2 polymorphisms of the GH receptor gene: an A-to-G transition in third position of codon 168 in exon 6 and a C-to-A transversion in the first position of codon 526 in exon 10. We further sequenced all coding exons and intron-exon boundaries in the most affected patients (nos. 6, 9, 11, 14, 15, 16, and 23). This analysis revealed a C-to-T transition in codon 161 of exon 6 in patient 23, which results in an amino acid change (Arg to Cys) in an heterozygous form in the patient and his father. In conclusion, the results of our study suggest that, in Chilean patients with idiopathic short stature, GH receptor gene mutations are uncommon, although we cannot exclude mutations that were missed by single-strand conformational analysis or mutations within introns or in the promoter regions of the GH receptor gene.