Genotypes and Haplotypes in the AXIN2 and TCF7L2 Genes are Associated With Susceptibility and With Clinicopathological Characteristics in Breast Cancer Patients.

Background: Breast cancer is a multifactorial disease whose genetic susceptibility is related to polymorphic variants of cell proliferation and migration pathways. Variants in AXIN2 and TCF7L2 in the Wnt-ß catenin pathway have been associated with different types of cancer; however, little is known about its role in breast cancer. This study tests the hypothesis of links between AXIN2 rs1133683 and rs2240308, and TCF7L2 rs7903146 and rs12255372 variants in breast cancer. Methods: Peripheral blood samples were obtained from 404 women (202 patients and 202 control females). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology was used to identify the gene variants. Results: The AXIN2 rs2240308 (C > T), and TCF7L2 rs7903146 (C > T) and rs12255372 (G > T) variants were associated with breast cancer and with age, TNM stage, and histologic-molecular subtype (p = 0.001). Likewise, the haplotype T-T in the TCF7L2 gene (rs7903146-rs12253372) was significantly related with breast cancer (OR = 2.66, 95%, CI = 1.64-4.30, p = 0.001). Conclusion: Our data show a link between AXIN2 rs2240308 and TCF7L2 rs7903146 and rs12255372 variants in breast cancer, and speculate this may be important in pathogenesis.

Distribution of IFITM3 polymorphism (dbSNP: rs12252) in mestizo populations in four states of Mexico.

Interferon-inducible transmembrane protein 3 (IFITM3) participates in the defense against viral infections. This study identified and compared the frequency of the IFITM3 rs12252 polymorphism in 410 individuals in western Mexico. The western Mexican allelic frequencies (frequency of the "C" allele = 0.18) differ from some American, East Asian and European populations.

Contribution of polymorphisms in the LEP, LEPR and RETN genes on serum leptin and resistin levels in young adults from Mexico.

Polymorphisms in the LEP (G-2548A and A19G), LEPR (A326G, A668G and G3057A) and RETN (C-420G and G+62A) genes were documented according to their association with alterations in biochemical parameters such as glucose, insulin and lipid profiles, along with serum leptin and resistin concentrations. The aim of the study was to establish any contribution of the G-2548A and A19G polymorphisms of the LEP gene, the A326G, A668G and G3057A polymorphisms of the LEPR gene, and the C-420G and G+62A polymorphisms of the RETN gene to serum leptin and resistin levels in Mexican young adults. Clinical and biochemical variables, serum leptin and resistin levels, and genotype profiles were analysed in 66 Mexican young adults. Seven polymorphisms in the LEP, LEPR and RETN genes were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analysis. Individuals carrying allele 3057A of the G3057A polymorphism in the LEPR gene showed significantly higher leptin concentrations than those bearing the genotype G/G (43.78 ± 39.11 vs 28.20 ± 14.12 ng/mL; p = 0.021). There were no associations of serum leptin or resistin levels according to the genotype of the other six analysed polymorphisms. Our results suggest that the allele 3057A of the LEPR G3057A polymorphism contributes to increased serum leptin levels in Mexican young adults.

Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer.

PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-node-metastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance. In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

TCF7L2 and CCND1 polymorphisms and its association with colorectal cancer in Mexican patients.

Accumulative evidence suggests that alterations due to mutations or genetic polymorphisms in the TCF7L2 and CCND1 genes, which are components of the Wnt signaling pathway, contributes to carcinogenesis. The present study was designated to clarify whether common single nucleotide polymorphisms (SNPs) of the transcription factor 7- like 2 (TCF7L2) and cyclin D1 (CCND1) genes are associated with colorectal cancer risk in Mexican patients. A case-control study including 197 colorectal cancer patients and 100 healthy subjects was conducted in a Mexican population. Identification of polymorphisms was made by the polymerase chain reaction-restriction fragment length polymorphism methodology. The association was calculated by the odds ratio (OR) test. The results demonstrate that patients with the T/T genotype for the rs12255372 polymorphism of the TCF7L2 gene present an increased colorectal cancer risk (OR=2.64, P=0.0236). Also, the risk analysis for Tumor-Nodule-Metastasis (TNM) stage and tumor location showed association with this polymorphism under the over-dominant model of inheritance (OR=1.75, P=0.0440). A similar relation was observed for the genotype T/T of the rs7903146 polymorphism and the rectal location of cancer (OR=7.57, P=0.0403). For the rs603965 polymorphism of the CCND1 gene, we observed a protection effect for the colon cancer location under the dominant model (OR=0.49, P=0.0477). These results reveal a significant role of the analyzed polymorphisms in the TCF7L2 and CCND1 genes on the susceptibility or protection for developing colorectal cancer in the Mexican population.

Tumor necrosis factor haplotype diversity in Mestizo and native populations of Mexico.

The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.

The -174G/C and -572G/C interleukin 6 promoter gene polymorphisms in mexican patients with rheumatoid arthritis: a case-control study.

OBJECTIVE: There is a lack of information about the genotype frequencies of IL-6 -174G/C and -572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 -174G/C and -572G/C polymorphisms in Mexican mestizo with RA. METHODS: We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 -174G/C and -572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. RESULTS: The genotype -174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype -572GG (54% in patients versus 60.8% in controls, P = 0.295). CONCLUSIONS: This is the first study to evaluate the association of -174G/C and -572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.

XV-2c/KM19 haplotypes analysis of cystic fibrosis patients from western Mexico.

The analysis of polymorphic markers within or closely linked to the cystic fibrosis transmembrane regulator (CFTR) gene is useful as a molecular tool for carrier detection of known and unknown mutations. To establish the association between mutations in the CFTR gene in western Mexican cystic fibrosis (CF) patients, the distribution of XV2c/KM19 haplotypes was analyzed by PCR and restriction enzyme digestion in 384 chromosomes from 74 CF patients, their unaffected parents, and normal subjects. The haplotype analysis revealed that haplotype B was present in 71.9% of CF chromosomes compared to 0% of non-CF chromosomes. The F508del and G542X mutations were strongly associated with haplotype B (96.7% and 100% of chromosomes, respectively). The haplotype distribution of the CF chromosomes carrying other CFTR mutations had a more heterogeneous background. Our results show that haplotype B is associated with CFTR mutations. Therefore, haplotype analysis is a suitable alternate strategy for screening CF patients with a heterogeneous clinical picture from populations with a high molecular heterogeneity where carrier detection programs are not available. In addition, it may be a helpful diagnostic tool for genetic counseling and carrier detection in the relatives of CF patients and in couples who are planning to have children.

Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia.

The etiology of preeclampsia is still a matter of controversy. An association between hyperhomocysteinemia and preeclamptic patients has been described. A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased plasma homocysteine concentrations. In addition, the polymorphism of gene encoding for Factor V Leiden G1691A is associated with a prothrombotic state in heterozygous subjects. Both mutations in these thrombophilic proteins appear to have different prevalence in the general population and in patients with preeclampsia/eclampsia (PE/E). We studied single nucleotide polymorphisms for MTHFR C677T and coagulation Factor V Leiden in 33 Mexican patients with PE/E as a genetic risk factor for these diseases, comparing with a normotensive pregnant control group. The genotype and allele frequencies of MTHFR C677T and Factor V Leiden mutations between Mexican women with PE/E and healthy controls were not different. We conclude that these polymorphisms do not contribute in the etiology of PE/E as it has been reported in other populations.

Association analysis of the Gln223Arg polymorphism in the human leptin receptor gene, and traits related to obesity in Mexican adolescents.

Polymorphisms of leptin receptor (LEPR) may contribute to a common form of obesity and, as a consequence, obesity-related diseases. We evaluated the potential role of genetic variation at the LEPR gene in heart sympathetic activity and other traits related to obesity in Mexican adolescents. Adolescents aged between 12 and 17 years, with steady body weight for the last 3 months were included. We evaluated anthropometric measurements, blood pressure, seric glucose, insulin, leptin levels, heart sympathetic activity (by electrocardiograph monitoring at rest), and the Gln223Arg and Pro1019Pro LEPR polymorphisms in each subject. In total, 103 adolescents (55 obese and 48 nonobese) were included. The group of obese adolescents showed higher sympathetic activity, blood pressure, glucose, insulin, and leptin levels. The genotype frequencies for the two polymorphisms were found to be in Hardy-Weinberg equilibrium. There was no difference in the genotype frequencies for Gln223Arg or Pro1019Pro polymorphisms between obese and nonobese adolescents. However, there was a higher prevalence of Gln223 allele among subjects with higher insulin levels (0.72 vs 0.57; P = 0.04 for adolescents with insulin levels higher and lower than 100 pmol/l, respectively). According to Gln223Arg polymorphism, those with Gln allele (Gln/Gln and Gln/Arg) had higher heart sympathetic activity, body fat percentage, and leptin levels. To conclude, our results support the hypothesis that Gln223Arg polymorphism of LEPR in Mexican adolescents is associated with haemodynamic and metabolic disturbances related to obesity.

DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group.

Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed. We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.

Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

Association analysis of polymorphisms in the interleukin-4 receptor (alpha) gene with atopic asthma in patients from western Mexico.

We undertook an association analysis between the ile50val, glu375ala, cys406arg, and ser761pro polymorphisms of the IL-4Ralpha gene and atopic asthma, total IgE levels and IL-4 serum levels in a population from western Mexico. We found that the ser761pro polymorphism was monomorphic for ser761, while there was no association between any of the other polymorphisms and the three phenotypes analysed.

[The detection of human papillomavirus 16, 18, 35 and 58 in cervical-uterine cancer and advanced degree of squamous intraepithelial lesions in Western Mexico: clinical-molecular correlation]. / Detección de papilomavirus humano tipos 16, 18, 35 y 58 en cáncer cervicouterino y lesiones escamosas intraepiteliales de alto grado en el occidente de México: correlación clínico-molecular.

The purposes of this study were to estimate the infection frequency of Human Papilomavirus (HPV) and to identify the viral types in patients with diagnosis of uterine cervical cancer (UCC) and High Grade Squamous Intraepitelial lesions (HGSILs), and to correlate the molecular findings versus HPV infection suggestive clinical findings. Biopsies from 50 patients (37 HGSILs and 13 UCC) histopathologically diagnosed were studied. The presence of HPV were detected by means of the polymerase chain reaction (PCR) using consensus primers for types 6, 11, 16, 18, 31, 33, 35, and 58 among others, as well as specific primers for some of them. The frequencies for HPV 16, 18, 33, 35, and 58 in HGSIL samples were 24.3, 2.7, 0, 5.4 and 16.2% respectively. In UCC samples were 61.5, 7.7, 0, 0 and 15.4% with significative differences only for HPV 16. Clinical findings (histologic, colposcopic and histopathologic), showed deficient diagnostic accuracy in the identification of HPV 16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV. These results are similar to those previously described in our country and the other populations, with the exception of HPV16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV 58 in our region. When analyzing clinical features with the presence of HPV DNA, we conclude that these are insufficient to discard or establish the possibility of HPV infection in patients with HGSIL's and UUC.

Detección de papilomavirus humano tipos 16, 18, 35 y 58 en cáncer cervicouterino y lesiones escamosas intraepiteliales de alto grado en el occidente de México: correlación clínico-molecular / Papilomavirus type 16, 18, 35 and 58 detection in cervicouterine cancer and high grade squamous intrapitelial lesions in México: Clinic-molecular-correlation

Los propósitos de este estudio fueron estimar la frecuencia de infección por papilomavirus humano (PVH) e identificar los tipos presentes en pacientes con diagnóstico de cáncer cerivicouterino (CaCu) y lesiones escamosas intraepiteliales de alto grado (LEIAG) y correlacionar los hallazgos moleculares contra los hallazgos clíncos sugestivos de infección por PVH. Se estudiaron biopsias provenientes de 50 pacientes (37 LEIAG y 13 CaCu) diagnosticadas histopatológicamente. Se detectó la presencia de PVH por medio de la reacción en cadena de la polimerasa (RCP) utilizando iniciadores consenso para los tipos 6, 11, 16, 18, 31, 33, 35 y 58 entre otros, así como iniciadores específicos para algunos tipos. Las frecuencias de infección para los PVH 16, 18, 33, 35 y 58 en las muestras de LEIAG fueron 24, 2, 0, 5 y 16 por ciento respectivamente. En las muestras de CaCu fueron 61, 7, 0, 0 y 15 por ciento encontrando diferencias significativas sólo para PVH 16. Los hallazgos clínicos (histológicos, colposcópicos e histopatológicos) mostraron una precisión diagnóstica deficiente en la identificación de PVH. Estos resultados son similares a aquellos informados en otras regiones de México con la excepción de la frecuencia de PVH 16 en LEIAG, la cual resultó menor y la frecuencia elevada de PVH 58 en nuestra región. Al contrastar los hallazgos colposcópicos, citológicos e histopatológicos con la presencia de DNA de PVH, concluimos que estos hallazgos son insuficientes para descartar o establecer la presencia de PVH en pacientes con LEIAG y CaCu.

Molecular identification of 7 human papillomavirus types in recurrent respiratory papillomatosis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is the most frequent benign neoplasm in childhood; it originates as a mild dysphonia and results in asphyxia. The RRP has been associated with an infection caused by human papillomavirus (HPV), mainly types 6 and 11, the latter being associated with more severe RRP. OBJECTIVES: To analyze the frequency of the association of RRP with the HPV types in our juvenile population and to classify it according to severity. DESIGN: Observational descriptive trial. MATERIALS AND METHODS: Forty-seven samples of paraffin-embedded papillomas, from 26 female and 21 male children (age range, 2 weeks to 17 years) were analyzed. DNA was isolated and a 188-base pair fragment was amplified from a consensus sequence in the E1 open reading frame of several HPVs by polymerase chain reaction. The corresponding band was recovered and reamplified. The fragment was digested with the restriction enzyme RsaI. The digestion products were compared with patterns of molecular weight markers for viral type identification. The patients' clinical records were reviewed, and RRP was classified as mild or aggressive. RESULTS: The presence of HPV types 6, 11, 16, 31, 33, 35, or 39 was confirmed in all the cases with different combinations. The chi(2) test showed no significant differences in clinical aggressiveness among the viral types. A logistic regression analysis demonstrated no association between clinical aggressiveness and any viral type or viral combination. CONCLUSION: These results show that RRP is caused by infection with HPV types 6 and 11 in addition to many other types, with no relationship between HPV type and clinical severity.

[Detection of Mycobacterium tuberculosis by polymerase chain reaction in a selected population in northwestern Mexico]. / Detección de Mycobacterium tuberculosis mediante la reacción en cadena de la polimerasa en una población seleccionada del noroccidente de México.

This study compares the detection of Mycobacterium tuberculosis through bacilloscopy (Ziehl-Neelsen stain), growth in Lowenstein-Jensen medium, and polymerase chain reaction (PCR) carried out with DNA taken directly from various types of samples. A total of 252 samples were analyzed (114 sputum, 96 urine, 15 cerebrospinal fluid, and 27 of other types) from 160 patients with any form of suspected tuberculosis who came to the Clinical Pathology Laboratory of the Specialties Hospital of the Western National Medical Center of the Mexican Social Security Institute. In all cases Ziehl-Neelsen stains were done, as were also cultures with Lowenstein-Jensen medium and PCR amplification of a segment of 285 base pairs specific to the M. tuberculosis complex. Of the 252 samples, with the culture, 18 were positive for nontuberculous mycobacteria. Of the 234 others, 12 (5.1%) were positive with the PCR and the culture, 174 (74.4%) negative in both tests, 47 (20.1%) positive with the PCR and negative with the culture, and 1 (0.4%) negative with the PCR and positive with the culture. Using the culture as the reference test, the PCR provided a sensitivity of 92.3%, a specificity of 78.7%, a positive predictive value of 20.3%, and a negative predictive value of 99.4%. The PCR detection limit with DNA taken from culture was 10 fg, equivalent to four or five mycobacteria. Also in comparison with the culture, the PCR correctly identified the totality of the mycobacteria of the M. tuberculosis complex. Taking the culture as the reference test, when analyzing just the sputum samples, the direct PCR provided a sensitivity of 90.9%, a specificity of 89.5%, a positive predictive value of 52.6%, and a negative predictive value of 98.7%. The PCR is a sensitive and specific technique for detecting the M. tuberculosis complex in both positive and negative bacilloscopy samples. A controlled PCR procedure makes it possible to establish or to exclude the diagnosis of tuberculosis in a time that is reduced from more than three weeks to just 24 to 48 hours. This is particularly useful when an early diagnosis is needed to establish a patient's prognosis or in organ transplant cases.

Urinary glycosaminoglycan excretion in healthy subjects and in patients with mucopolysaccharidoses.

BACKGROUND: The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of enzymes catalyzing the stepwise degradation of glycosaminoglycans (GAGs), and are transmitted in an autosomal recessive manner, except for Hunter syndrome. METHODS: The levels of GAGs in 150 healthy subjects and 33 patients with MPS were determined, and results were expressed as milligrams of GAGs per grams of creatinine. RESULTS: We found that this ratio decreased with age during the first 15 years of life, but had a constant low rate between the ages of 17-40 years in healthy individuals. A different tendency was present in patients with MPS, because levels of GAG excretion in this group were higher (by four standard deviations up) compared with healthy individuals. The electrophoretic patterns of urinary GAGs in healthy subjects showed that the higher levels detected in urine were chondroitin sulfate (4 and 6) and a smaller quantity of dermatan sulfate, but in each MPS type its characteristic pattern was identified. CONCLUSIONS: This is a simple, reproducible method suitable for routine laboratory separation, identification, and quantity of urinary GAGs and for diagnosing MPS syndromes.

Molecular analysis of northwestern Mexican patients with cystic fibrosis: screening of 10 known mutations. Mutations in brief no. 185. Online.

We have analyzed 45 unrelated Northwestern Mexican patients with Cystic Fibrosis for 10 known CF mutations (DF508, G542X, G551D. R553X, W1282X, NI303K, R334W, R347H, S549R, and R1162X). Screening was performed on exons 7, 10, 11, 19, 20 and 21 using standard methods such as polymerase chain reactions, reverse dot blot hybridization (non-radioactive), and restriction enzyme digestion. The analysis for these ten mutations permitted the identification of only two mutations in 37.7% of CF chromosomes in this sample. The major mutation, delta F508, accounts for 34.4% of CF chromosomes. Of the 45 CF patients 9 (20.0%) were homozygous delta F508 deletion, 11 (24.4%) were heterozygous for the delta F508 mutation and an unknown mutation. One additional mutation G542X was also found in 3 chromosomes in our population (3.3%). Two patients were documented to be a compound heterozygote for DF508/G542X, and other one heterozygous for G542X and an unknown mutation. Therefore 62.2% of chromosomes remain uncharacterized.

Mucopolysaccharidoses type II: enzymatic activity and quantitative and qualitative studies of urinary glycosaminoglycans in five patients.

Five patients presenting Hunter's syndrome were biochemically studied. Quantification of urinary glycosaminoglycans (GAGs), electrophoretic characterization and correlation with enzymatic activity in leucocytes were carried out. In all cases, urinary GAGs/creatinine ratio was increased. Electrophoresis revealed the presence of heparan sulfate (HS) and dermatan sulfate (DS) in four cases (80%), but in the remaining patient, only DS was present. In all patients, deficient enzymatic activity was demonstrated. These results show evidences of biochemical differences in this syndrome.