Eliakym Arámbula-Meraz

Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients.

BackgroundPapillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1–4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans.MethodsTo understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population.ResultsPatients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T >; G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C >; T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T >; G); and 11.11%, 8.82% and 9.00% for T (c.458C >; T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33.ConclusionsThe novel loss-of function mutation of CTSC gene (c.203 T >; G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.

Tetralogy of Fallot associated with macrocephaly-capillary malformation syndrome: a case report and review of the literature

IntroductionMacrocephaly-capillary malformation syndrome is characterized by cutaneous vascular lesions, including cutis marmorata telangiectatica and hemangiomas, associated with congenital anomalies, including macrocephaly, macrosomia, asymmetry and mental retardation. In addition to these cardinal signs, several other clinical conditions have been reported in people with this condition. However, to the best of our knowledge, the presence of tetralogy of Fallot has not previously been reported in association with this syndrome.Case presentationWe present a case of a Mexican newborn girl with tetralogy of Fallot associated with macrocephaly-capillary malformation. We discuss the clinical treatment of the patient and its consequences.ConclusionSince physiologic cutis marmorata is a common condition in newborns, the information provided in this report could be helpful in future cases in preventing severe clinical consequences or sudden death in patients with similar symptoms.

Glucose-6-phosphate dehydrogenase deficiency in northern Mexico and description of a novel mutation

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD-deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% (n = 1993); the mutations in 86% of these samples were G6PD A−202A/376G, G6PD A−376G/968C and G6PD Santamaria376G/542T. Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country (P = 0.48336), and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF193A>G (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described.

Polimorfismo 677CT del gen de la metilentetradihidrofolato reductasa y cardiopatias congenitas aisladas en poblacion mexicana

INTRODUCTION AND OBJECTIVES The frequency of the 677C>T mutation in the methylenetetrahydrofolate reductase gene in Mexico is one of the highest worldwide. Some studies have shown that both the homozygous state of this mutation and a high homocysteine concentration are associated with congenital heart disease. The aim of this study was to determine whether this association exists in the Mexican population. METHODS Genotypes were analyzed in 60 patients with congenital heart disease and in their mothers, and the levels of homocysteine were determined in the latter group. The genotypes were compared with those of a control group (n=62) and of their mothers. All the possible mother-child genotype combinations were also compared. RESULTS There were no significant differences in allele or genotype frequencies between the patients with congenital heart disease and the controls or their respective mothers (P>.05). Although no significant differences were observed when the homocysteine concentrations in the presence of the CC or the TT genotype were compared, a clear trend was observed (P=.0621). We found no significant differences in homocysteine concentrations in relation to folic acid intake. The study cases and controls did not differ in terms of the possible combinations of mother-child genotypes. CONCLUSIONS The frequencies obtained were consistent with those reported for Mexico. No significant differences were found between groups. Nor did we find any association between TT mutations in both the mother and child and hyperhomocysteinemia. There was no evidence of an association between any of the mother-child genotype combinations and congenital heart disease. Similar studies with larger numbers of patients are required to confirm or refute some of the trends observed in this report.

Parasitaemia levels in Plasmodium chabaudi infected-mice modify IFN-γ and IL-10 expression after a homologous or heterologous challenge

CB6F1 mice infected with the nonlethal Plasmodium chabaudi chabaudi AS suffer parasitaemia levels up to 40% (full parasitaemia, FP) and develop both homologous and heterologous (against the lethal Plasmodium yoelii 17XL) protective immunity. However, if mice are treated with anti‐malarial drug when parasitaemia is below 10% (low parasitaemia, LP), they only develop homologous immunity. For the better understanding of this interesting dissociation related to the degree of parasitaemia, in this work, we studied the genetic expression of some cytokines. We found that during primary parasitaemia both FP and LP mice showed at first a TNF‐α, IL‐2 and IFN‐γ response which is followed by an IL‐4 and IL‐10 response. When FP and LP mice were challenged with either the homologous (FP + AS and LP + AS mice) or the heterologous parasite (FP + 17XL and LP + 17XL mice), we observed that LP + 17XL mice, which failed to develop heterologous immunity and succumbed to the challenge, showed a stronger IFN‐γ and a weaker IL‐10 expression than FP + 17XL mice, which developed heterologous immunity and survived the challenge. The importance and the possible implications of these findings are discussed.

47,XXY/48,XXXY/49,XXXXY mosaic with hydrocephaly: a case report and review of the literature

Klinefelters syndrome is a frequent genetic sexual alteration in males, associated with the 47,XXY aneuploidy. Several syndrome variants are caused by different X and Y polysomy and mosaicisms, including the 49,XXXXY condition described by some authors as Fraccaros syndrome. Mosaics with three or more different chromosomal lines are very rare. Here, we describe a case with XXY/XXXY/XXXXY mosaic in a newborn with clinical features of Fraccaros syndrome, but also with obstructive hydrocephaly which has not been reported previously.

The paternal polymorphism rs5370 in the EDN1 gene decreases the risk of preeclampsia

OBJECTIVE To evaluate whether the maternal, paternal or the combined maternal/paternal contribution of SNP rs5370 of the EDN1 gene is associated with preeclampsia and drove its expression in placenta. STUDY DESIGN This case-control study included 61 preeclamptic patients and their partners and 49 healthy pregnant women and their partners. The population was sub-divided into three groups: women-only, men-only and combined (women/men). The analysis included genotyping of rs5370 in mothers and fathers and evaluating the expression profile of the EDN1 gene in placenta. Comparisons of categorical variables were performed using chi-square and/or Fishers exact tests. The intergroup comparisons were analysed with the Mann-Whitney U test. The association between the polymorphism and the disease was evaluated through multivariate regression analysis. Spearmans correlation was performed to test the relationship between pre-gestational history and clinical features of the affected patients with EDN1 gene expression. RESULTS The analysis of paternal risk factors associated with preeclampsia revealed no differences between groups. A negative association between SNP rs5370 and preeclampsia was found in men group (OR 0.42; CI 95% 0.18-0.94, p=0.034) but not in women or combined groups. The adjustment for paternal protective factors increased the observed negative association, and the opposite was observed in the presence of paternal risk factors. The expression of the EDN1 gene in the placenta was significantly higher in the group of cases and was not associated with the rs5370 polymorphism. CONCLUSION The paternal rs5370 polymorphism decreases the risk for preeclampsia and is not associated with placental expression of the EDN1 gene.

De novo dir dup/del of 18q characterized by SNP arrays and FISH in a girl child with mixed phenotypes

1Laboratorio de Citogenomica y Microarreglos, Departamento de Bioquimica y Medicina Molecular, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico 2Unidad de Biologia Molecular, Genomica y Secuenciacion, Centro de Investigacion y Desarrollo en Ciencias de la Salud, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico 3Laboratorio de Genetica, Hospital General de Culiacan, SSS, Culiacan 80019, Sinaloa, Mexico 4Centro de Rehabilitacion y Educacion Especial (CREE), DIF, Sinaloa 80019, Mexico 5Division de Genetica, Instituto Mexicano del Seguro Social, CIBO, Guadalajara 44340, Mexico 6Doctorado en Genetica Humana, CUCS, Universidad de Guadalajara, Guadalajara 44340, Mexico 7Laboratorio de Genetica y Biologia Molecular, FCQB, Universidad Autonoma de Sinaloa, Sinaloa 80019, Mexico 8Laboratorio de Genetica Humana, Unidad de Investigacion, Facultad de Medicina, Universidad Autonoma de Sinaloa, Sinaloa 80019, Mexico

S1249 Frequency of the Genetic Polymorphism Xbal of ApolipoproteíNa B-100 (apo B-100) in Patients With Gallblader Lithiasis of a Population Sinaloa, Mexico: Comparative Study

phospholipids, higher CSI, lower nucleation time and higher concentration of deoxicholic acid when compared with control group. Conclusions: Our results showed the composition of gallstones is similar to developed country in according with the recent improvement of social condition of our country and with literature findings. Lithogenic factors were presented in the bile of patients with cholesterol gallstones and correlate with the presence of predictors factors for the gallstone formation in our population.