Browsing by Author "Poggi, Helena"
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Item ALS deficiency caused by an exon 2 deletion and a novel missense variant in the gene encoding ALS(2019) Dominguez, Gonzalo; Poggi, Helena; Arancibia, Mónica; Benavides, Felipe; Martínez, AlejandroContext ALS deficiency (ACLSD), caused by mutations in IGFALS, is characterized by a mild short stature, low concentrations of IGF-I and IGFBP-3, and a normal growth hormone (GH) stimulation test response. To our knowledge, no larger deletions have been reported. Case description A 17-year-old adolescent male was evaluated due to delayed puberty and short stature. He had a height of 154.4 cm (SDS -2.84), a weight of 53.3 kg (SDS -1.41), a BMI of 22.4 kg/m2 (SDS +0.31), a Tanner 2 pubertal stage with a testicular volume of 10 mL, and a bone age of 16 years (SDS -1.33). After biochemical evaluation, low IGF-I levels, undetectable IGFBP-3 levels, and a normal response to the GH stimulation test were observed, suggesting GH insensitivity. ACLSD was confirmed by ALS measurement (116 ng/mL, SDS -3.19) and genetic analysis of IGFALS. An apparently homozygous missense variant, p. Pro624Leu, was found in exon 2 of the proband; this mutation was observed on one allele of the proband's father but was absent in the mother and siblings. Deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA) was consistent with a deletion encompassing a significant part of exon 2 on one allele in the proband and in his mother and siblings. Conclusion This is the first report of a large deletion in a patient with ACLSD. Deletion/duplication analysis should be considered in the genetic study of ACLSD, especially when homozygosity for a pathogenic variant cannot be confirmed by the study of the parents or when no variants are found but ALS concentrations are very low.Item Efecto de las variantes de VKORC1 y CYP2C9 sobre la dosis de anticoagulantes orales en individuos chilenos(Sociedad Medica de Santiago, 2015) Benavides, Felipe; Grossman, Nicole; Poggi, Helena; Nieto, Elena; Bertrán, Antonio; Araos, Daniel; Vásquez, Marcos; Ibarra, Ignaz; Caceres, Felipe; Espinoza, Karena; Lagos, Marcela; Repetto, GabrielaBACKGROUND: The dose of oral anticoagulants (OAC) shows great variability among patients. Pharmacogenetic studies have shown that common variants in genes CYP2C9 (*2 and *3) and VKORC1 (-1639G>A) are associated with lower requirements of OAC. AIM: To study the association between average maintenance doses of oral anticoagulant therapy required to maintain a stable INR and CYP2C9 and VKORC1 gene variants in Chilean adults. MATERIAL AND METHODS: Prospective study of patients on anticoagulant treatment and with a stable international normalized ratio (INR) for prothrombin time for at least three months. Patients were classified as having high or low acenocoumarol or warfarin requirements. Peripheral blood DNA genotyping was performed by polymerase chain reaction and restriction fragment polymorphism or sequencing and electrophoresis. RESULTS: The study included 185 patients, 125 on acenocoumarol and 60 on warfarin. Patients with VKORC1-1639A allele were more likely to require lower doses of both drugs than patients with the G allele (Odds ratio [OR] for acenocoumarol 9.06, and OR for warfarin = 18.7). There was no association between CYP2C9*2 and*3 and acenocoumarol or warfarin requirements. CONCLUSIONS: There is an association between VKORC1-1639A variant and anticoagulant doses.