Browsing by Author "Puga, Alonso"
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Item Angiotensin-converting enzyme insertion/deletion polymorphism is associated with severe hypoxemia in pediatric ARDS(Springer, 2012) Cruces, Pablo; Puga, Alonso; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristobal; Wilhelm, Jan; Repetto, GabrielaPURPOSE: The D allele of the insertion/deletion (I/D) polymorphism of a 287-bp sequence in the angiotensin-converting enzyme (ACE) gene has been associated with an increased activity of this enzyme. Its role in susceptibility to acute respiratory distress syndrome (ARDS) has not been well defined. We hypothesized that ACE I/D genotype in pediatrics is associated with ARDS and plasma levels of angiotensin II. METHODS: Prospective case-control study in patients under 15 years of age from a mixed Chilean population. Sixty patients with ARDS and 60 controls were included. Association between ACE genotype and ARDS was evaluated as the primary outcome; mortality and severe hypoxemia were examined as secondary outcomes. Plasma angiotensin-II concentration was measured by immunoassay at admission. RESULTS: Frequency of ACE I/D genotype was similar in ARDS and control groups (p = 0.18). In the ARDS group, severe hypoxemia was less frequent in D allele carriers (p < 0.05). Plasma angiotensin-II levels were associated with genotype in the ARDS group, but not controls, being higher in D allele carriers (p = 0.016). CONCLUSION: These data do not support the association between ACE I/D genotype and ARDS, although severe hypoxemia was less frequent in D allele carriers. ACE I/D polymorphism modified angiotensin-II levels in pediatric ARDS, but its pathogenic role is not well understood and needs to be addressed in future studies.Item Cystic fibrosis in Chilean patients: Analysis of 36 common CFTR gene mutations(Elsevier, 2012) Collaborative Group of the Chilean National Cystic Fibrosis Program; Lay-Son, Guillermo; Puga, Alonso; Astudillo, Pedro; Repetto, GabrielaBACKGROUND: CFTR gene mutations have worldwide differences in prevalence and data on Chilean patients is scarce. METHODS: We studied 36 of the most common CFTR mutations in Chilean patients from the CF National Program [Programa Nacional de Fibrosis Quística (PNFQ)] of the Ministry of Health of Chile. RESULTS: Two hundred and eighty-nine patients were studied. Fourteen different mutations were identified with an overall allele detection rate of 42.0%. Mutations with frequencies greater than 1% were p.F508del (30.3% of alleles), p.R334W (3.3%), p.G542X (2.4%), c.3849+10Kb C>T (1.7%), and p.R553X (1.2%). A north to south geographical gradient was observed in the overall rate of detection. CONCLUSIONS: Southern European CFTR mutations predominate in the Chilean population, but a high percentage of alleles remain unknown. Geographical heterogeneity could be explained in part by admixture. Complementary analyses are necessary to allow for effective genetic counselling and improve cost-effectiveness of screening and diagnostic tests.Item Diagnóstico de intolerancia a la lactosa en adultos: rendimiento comparativo de la clínica, test de hidrógeno espirado y test genético(Sociedad Medica de Santiago, 2012) Rollan, Antonio; Vial, Cecilia; Quesada, Soledad; Espinoza, Karena; Hatton, Mary; Puga, Alonso; Repetto, GabrielaBackground: Genetically programmed adult-type hypolactasia affects 56% of Chilean population. Ideally, diagnosis should be confirmed. Aim: To compare diagnostic yield of genetic test, hydrogen (H2) expiratory test and a validated symptomatic structured survey (SS). Material and Methods: Patients submitted to H2 test answered a historic (anamnestic) and current SS (after the ingestion of 25 g of lactose). A blood sample was obtained for determination of genetic polymorphisms C/T_13910, C/G_13907 and G/A_22018 by polymerase chain reaction. The gold standard for diagnosis of lactose intolerance (LI) was the agreement of at least two of three tests. Results: Sixty-one participants aged 39 ± 12 years (21 males), were studied. Anamnestic SS was diagnostic of LI in all cases (score > 7), while current SS detected LI in 27/61 (46%). H2 test (an increase > 15 ppm after ingestion of 25 g of lactose) showed LI in 31/61 (51%). The locus C/G_13907 showed no polymorphism and locus G/A_22018 was in complete linkage disequilibrium with C/T_13910. Genotype C/C_13910, associated to hypolactasia, was present in 30/58 (52%). According to the gold-standard, 32/61 (52.5%) patients were diagnosed as LI. Sensitivity and specificity were, respectively, 79% and 69% for current SS, 93% and 93% for H2 test and 97% and 93% for the genetic test. The last two showed a positive likelihood ratio (LR) > 10 and a negative LR < 0.1, figures within the range considered clinically useful. Conclusions: Genotype C/C_13910 is responsible for hypolactasia in this population. Anamnestic report of symptoms after milk ingestion and symptoms after lactose ingestion, are not accurate enough. H2 and genetic tests are simple and similarly accurate to diagnose lactose intolerance in adults.Item Evaluación de mutaciones en los genes GJB2 y GJB6 en pacientes con sordera congénita identificados mediante screening neonatal(2012) López, Gabriela; Puga, Alonso; Pittaluga, Enrica; Bustamante, Loretho; Godoy, Cristián; Repetto, GabrielaLa hipoacusia neurosensorial congénita es una patología frecuente que si no es detectada y tratada oportunamente genera alteraciones en el desarrollo del niño. Desde el año 2005 se lleva a cabo en el Complejo Hospitalario Dr. Sótero del Río un programa de screening auditivo universal para la detección precoz de esta patología. La mayor parte de los défi cits auditivos congénitos son genéticos. La etiología más común son las mutaciones en los genes GJB2 y GJB6, que codifi can para proteínas “gap junction” que permiten la traducción del sonido en el oído interno. Objetivo: Evaluar la presencia de mutaciones de los genes GJB2 y GJB6 en una población de niños diagnosticados con hipoacusia congénita en el Complejo Hospitalario Dr. Sótero del Río a través del programa de screening auditivo universal. Pacientes y Método: Se evaluaron 8 pacientes con hipoacusia congénita neurosensorial no sindrómica. Se extrajo ADN genómico de hisopado de mucosa bucal y se realizó PCR para identifi car la mutación 35delG en GJB2, seguida de secuenciación de este gen, y PCR para 2 deleciones del gen GJB6. Resultados: Dos pacientes fueron heterocigotos para la mutación 35delG en GJB2, siendo sus otros alelos normales. Dos fueron heterocigotos para el polimorfi smo V27I; uno acompañado por la variante p.A148A (c.444 C > A). Se encontró además un paciente con una mutación no descrita anteriormente (c.4360 C>T) en el intrón 1 de GJB2, siendo su segundo alelo normal. No se identifi caron mutaciones en GJB6. Conclusiones: En este grupo de niños estudiados se encontró mutaciones en el gen GJB2, causantes de sordera neurosensorial congénitaItem Growth in Chilean infants with chromosome 22q11 microdeletion syndrome(John Wiley & Sons, 2012) Guzman, Maria; Delgado, Iris; Lay-Son, Guillermo; Williams, Edward; Puga, Alonso; Repetto, GabrielaChromosome 22q11 microdeletion syndrome has a wide range of clinical manifestations including congenital heart malformations, palatal defects, endocrine abnormalities, immunologic deficits, learning difficulties, and an increased predisposition to psychiatric disease. Short stature and poor weight gain in infancy are common findings and are usually seen in the absence of hormone deficiencies. An increased frequency of obesity has been observed in adolescents and adults. We generated gender-specific growth curves from 0 to 24 months of age, based on 479 length and 475 weight measurements from 138 Chilean patients with 22q11 deletion. Final adult height and weight on 25 individuals were analyzed. The 10th, 50th, and 90th centile-smoothed curves for infants were built using the LMS method and compared with World Health Organization Child Growth Standards. The 50th centile for length in the deleted patients was slightly lower than the 10th centile of WHO standards in boys and girls. The same was observed for weight, although a trend toward a gradual increase near 2 years of age was observed, particularly in boys. Average adult height was 152 cm (ranging from 143 to 162 cm) in females, corresponding to the 10th centiles of WHO standards, and 166 cm for males (160-172 cm), at the 20th centile of WHO standards. A third of the adult females and none of the males had body mass index (BMI) greater than 25. The curves should be useful to monitor growth in infants with 22q11 microdeletion syndrome.Item Palate abnormalities in Chilean patients with chromosome 22q11 microdeletion syndrome(Elsevier, 2012) Lay-Son, Guillermo; Palomares, Mirta; Guzman, Luisa; Vasquez, Marcos; Puga, Alonso; Repetto, GabrielaOBJECTIVE: Chromosome 22q11 microdeletion syndrome (del22q11) is the most frequent microdeletion syndrome in humans, with an estimated incidence of 1/4000. It is recognized as a common identifiable cause of cleft palate. We characterized palatal abnormalities in a large cohort of Chilean patients with del22q11. METHODS: Patients with the deletion were evaluated by geneticists and speech pathologists, including nasopharyngoscopy when indicated. Comparisons between groups with and without palatal abnormalities were performed using Fisher's exact test and Mann-Whitney U test. RESULTS: Two hundred and one patients were included in the study. Palate abnormalities were present in 154 patients (76.6%). The most frequent finding was submucous cleft palate (both classic and occult forms) seen in 80 patients (39.8% of the total group). Overt cleft palate or cleft lip/palate was seen in 30 patients (14.9%). Patients without palate abnormalities had significantly greater frequency of congenital heart disease and higher mortality. CONCLUSIONS: Our data show a high frequency of palate abnormalities without significant association with congenital heart disease. The most common types of palate defects seen in this series are usually not evident on physical examination and thus require a high index of suspicion and active evaluation through nasopharyngoscopy.Item XV-2c and KM 19 haplotype analysis in Chilean patients with cystic fibrosis and unknown CFTR gene mutations(Sociedad de Biología de Chile, 2007) Repetto, Gabriela; Puga, Alonso; Delgado, IrisCystic fibrosis (CF) is caused by mutations in the CFTR gene. More than 1600 mutations have been described, with frequencies that differ worldwide according to the ethnic origin of patients. A small group of mutations are recurrent on several populations. It has been shown that they each tend occur on specific chromosome 7 haplotypes, supporting the notion of a single origin for them. Less than 50% of mutations in Chilean patients have been identified to date. To indirectly assess the possible presence of a predominant founder mutation in the remaining unknown alíeles, we evaluated 2 polymorphic markers, XV-2c and KM.19, tightly linked to the CFTR locus. The study was done in Chilean CF patients with unknown or deltΔF508 (ΔF508) CFTR mutations and their haplotypes were compared to affected family-based controls. ΔF508 showed marked linkage disequilibrium with XV-2c/KM.19 haplotype B, with 90% of alíeles on that haplotype. There was no difference in haplotype distribution between unknown mutations and normal controls. These results support a European origin for ΔF508 alíeles in Chilean patients, and make unlikely the presence of a predominant founder mutation in the so-far unknown alíeles.