Introduction: Due to the high frequency of C282Y and H63D mutations in the HFE gene, promoter type 1 hemochromatosis, and mutations S or Z causing the deficiency of alpha-1-antitrypsin (def-A1AT), studies have shown their coexistence in several patients. As a result, many scientists consider mutations in the HFE gene as a possible contributor to the development of hepatic events in patients with A1AT-def. Aim: To determine the frequency of C268Y and H63D mutations in patients with liver disease and presumptive diagnosis of A1AT-def. Materials and methods: We conducted a descriptive study that involved 65 patients with liver disease who were referred to the Molecular Biology Laboratory of the National Center of Medical Genetics for the molecular diagnosis of S and Z mutations of the gene for alpha-1 antitrypsin. We used the polymerase chain reaction method with polymorphisms in the sizes of the restriction fragments (PCR-RFLP). Results: The frequency of C282Y and H63D mutations of the HFE gene in patients with presumptive diagnosis of deficiency of alpha-1 antitrypsin was 5.3% and 17% respectively. Conclusions: this study showed that the frequency of these two mutations in Cuban population is high. We also observed that both of them, even in heterozygous state, seem to play a main role in the development of different diseases.

Introducción: debido a la alta frecuencia de las mutaciones C282Y y H63D del gen HFE, promotor de la hemocromatosis tipo 1 y de las mutaciones S o Z, causantes de la deficiencia de alfa-1-antitripsina (def-A1AT), se han reportado su coexistencia en varios pacientes, por lo que algunos autores han mencionado a las mutaciones en el gen HFE como posible contribuyente al desarrollo de las manifestaciones hepáticas en pacientes con def-A1AT. Objetivo: determinar la frecuencia de las mutaciones C268Y y H63D en pacientes con hepatopatías y diagnóstico presuntivo de def-A1AT. Materiales y métodos: se realizó un estudio descriptivo, conformado por 65 pacientes con hepatopatías, remitidos al laboratorio de biología molecular del Centro Nacional de Genética Médica, para el diagnóstico molecular de las mutaciones S y Z del gen de la alfa-1-antitripsina. Para la amplificación de las mutaciones C282Y y H63D se empleó el método de reacción en cadena de la polimerasa, con polimorfismos en los tamaños de los fragmentos de restricción (PCR-RFLP). Resultados: la frecuencia de las mutaciones C282Y y H63D del gen HFE en los pacientes con diagnostico presuntivo de deficiencia de alfa-1-antitripsina fue de 5,3 % y 17 %, respectivamente. Conclusiones: este estudio mostró que la frecuencia de estas dos mutaciones en la población cubana es alta. Igualmente, se pudo apreciar que ambas mutaciones, aun en estado heterocigoto, parecen jugar un papel fundamental en el desarrollo de diferentes patologías.

INTRODUCTION:Cystic fibrosis is a multisystem autosomal recessive disease with wide variability in clinical severity. It is incurable and characterized by elevated and premature mortality, as well as poor quality of life. Its frequency, lethality and devastating impact on both the physical and psychological wellbeing of patients and their families, make it a serious health problem. Its frequency in Cuba is 1 in 9862 live births, where marked molecular heterogeneity of the CFTR gene makes molecular diagnosis difficult. Six mutations have been identified that together enable molecular characterization of only 55.5% of cystic fibrosis chromosomes. This paper presents national results of antenatal diagnostic testing, using direct and indirect methods, for detection of cystic fibrosis. OBJECTIVE: Characterize the Cuban public health system's experience with antenatal molecular testing for cystic fibrosis from 1988 through 2011. METHODS: A retrospective descriptive study was conducted with results of antenatal diagnostic testing of amniotic fluid, performed nationwide from 1988 through 2011, for 108 fetuses of couples with some risk of having children affected by cystic fibrosis, who requested testing. Polymerase chain reaction detected mutations p.F508del, p.G542X, p.R1162X, p.R334W, p.R553X and c.3120+1G>A, and markers XV2C and KM19. Data were analyzed using absolute frequencies and percentages, and presented in tables. RESULTS: For 93 cases (86.1%), testing for cystic fibrosis was done using direct analysis of mutations p.F508del, p.G542X, p.R1162X, p.R334W, p.R553X and c.3120+1G>A; five cases (4.6%) were tested indirectly using markers XV2C/Taq I and KM19/Pst I; and 10 (9.3%) were tested using a combination of the two methods. A total of 72 diagnoses (66.7% of studies done) were concluded, of which there were 20 healthy fetuses, 16 affected, 27 carrier, and 9 who were either healthy or carriers of an unknown mutation. CONCLUSIONS: Direct or indirect molecular study was successfully used in over half of antenatal tests requested by couples throughout Cuba at risk of having children affected by cystic fibrosis, which is of great social value because of CF's burden on affected persons and their families.