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ABSTRACT: Bone marrow samples from children with acute lymphoblastic leukemia were analyzed for the expression of RUNX1a/b/c isoforms. Obtained patterns were associated with genetic abnormalities and the expression of the RUNX1 regulated gene BLK. RUNX1c was present in all patients, but the expected over-expression of RUNX1a was not observed. Over-expression of total RUNT domain isoforms was detected in patients with extra RUNX1 copies, and unexpectedly, in those with t(4;11). Only expression of the total RUNT domain-containing isoforms and BLK presented positive correlation. Results suggest a more complex role of RUNX1 in leukemogenesis than the proposed antagonism between the isoforms.
Leukemia research 06/2012; 36(9):1105-11. · 2.36 Impact Factor
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Clinical Endocrinology 06/2011; 76(1):148-50. · 3.17 Impact Factor
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ABSTRACT: Pompe disease or glycogen-storage disease type 2 (GSD2, OMIM 232300) is an autosomal recessive disorder caused by mutations in the acid alpha-glucosidase gene. Late-onset GSD2 resembles some limb-girdle and Becker muscular dystrophies. The screening of GSD2 through the measurement of acid alpha-glucosidase activity in dried blood spots was applied to a selected sample of 5 Mexican patients with proximal myopathies of unknown etiology. Only 1 male patient showed a low level of acid alpha-glucosidase activity and a compound heterozygote genotype for the c.-32-13T>G splicing mutation present in most white late-onset Pompe disease cases and the novel mutation p.C558S. To our knowledge, this is the first report of a Mexican patient with late-onset GSD2. The identification of c.-32-13T>G in our patient could reflect the genetic contribution of European ancestry to the Mexican population. The enzymatic screening of GSD2 could be justified in patients with myopathies of unknown etiology.
Journal of child neurology 03/2010; 25(8):1034-7. · 1.59 Impact Factor
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ABSTRACT: Duchenne muscular dystrophy (DMD) is the most frequent inherited and lethal neuromuscular disorder in humans. Molecular prenatal diagnosis of DMD through amniocentesis is a real preventive reproductive option in our country, although experience with chorionic villus sampling is still limited (CVS).
Perform the first prenatal diagnosis in an obligate DMD carrier woman in Mexico by CVS.
CVS was performed in an obligate DMD carrier woman in which no partial intragenic deletions were present but a haplotype at-risk was identified. Cytogenetic analysis with GTG banding was performed and genomic DNA extraction from CVS sample was done without culture. Fetal gender assignment was achieved by ultrasonography at 12 weeks of gestation and confirmed by PCR amplification of two Y chromosome-linked loci (SRY and DYS389I/II). Identification of the DMD haplotype at-risk in the fetus was done through analysis of the intragenic markers pERT87.8/TaqI and pERT87.15/Xmnl.
Absence of PCR products corresponding to Y chromosome-linked loci in DNA CVS sample was compatible with a female fetus; it was confirmed later by cytogenetic study and prenatal ultrasound follow-up. Linkage analysis reveals that the female fetus inherited the DMD haplotype at-risk. We did not identify any maternal DNA contamination in CVS molecular analysis and these results were postnatally confirmed in DNA obtained from buccal cells.
Molecular prenatal diagnosis through chorionic villus sampling could be an early reproductive prevention strategy applicable to Duchenne/Becker muscular dystrophy carrier women in our country.
Ginecología y obstetricia de México 03/2009; 77(2):103-9.
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ABSTRACT: Identify CTNS gene mutations in nephropathic cystinosis Mexican patients. Subjects and Methods: Eleven patients were included, nine presenting infantile nephropathic cystinosis and two siblings with the juvenile phenotype. The common 57-kb deletion was detected by multiplex PCR using large deletion marker-2 (LDM-2)/exon 4 set primers. Those alleles negative for 57-kb deletion were screened by single strand confirmation polymorphism (SSCP) and subsequent direct sequencing.
In our sample, five mutations previously reported are identified: 57-kb deletion, EX4_EX5del, c.985_986insA, c.357_360delGACT, and c.537_557del. We detect a false assignation of 57-kb deletion homozygous genotype by using the LDM-2/exon 4 primers. In addition, four novel and severe mutations are identified: c.379delC, c.1090_1093delACCAinsCG, c.986C>G (p.T216R), and c.400+5G>A.
Our sample of Mexican patients display allelic heterogeneity as compared to European or North American cystinosis cases. The identification of novel mutations might suggest the presence of exclusive American CTNS alleles in Mexican population. In order to prevent the false positive assignation of 57-kb deletion genotype, as caused by the presence of another type of intragenic CTNS gross deletion, we propose to analyze a different control CTNS exon to those originally reported in both LDM multiplex PCR assays, especially when parental DNA samples are not available.
Genetic Testing 10/2008; 12(3):409-14. · 1.17 Impact Factor
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ABSTRACT: Paired box gene 6 (PAX6) heterozygous mutations are well known to cause congenital non-syndromic aniridia. These mutations produce primarily protein truncations and have been identified in approximately 40%-80% of all aniridia cases worldwide. In Mexico, there is only one previous report describing three intragenic deletions in five cases. In this study, we further analyze PAX6 variants in a group of Mexican aniridia patients and describe associated ocular findings.
We evaluated 30 nonrelated probands from two referral hospitals. Mutations were detected by single-strand conformation polymorphism (SSCP) and direct sequencing, and novel missense mutations and intronic changes were analyzed by in silico analysis. One intronic variation (IVS2+9G>A), which in silico analysis suggested had no pathological effects, was searched in 103 unaffected controls.
Almost all cases exhibited phenotypes that were at the severe end of the aniridia spectrum with associated ocular alterations such as nystagmus, macular hypoplasia, and congenital cataracts. The mutation detection rate was 30%. Eight different mutations were identified: four (c.184_188dupGAGAC, c.361T>C, c.879dupC, and c.277G>A) were novel, and four (c.969C>T, IVS6+1G>C, c.853delC, and IVS7-2A>G) have been previously reported. The substitution at position 969 was observed in two patients. None of the intragenic deletions previously reported in Mexican patients were found. Most of the mutations detected predict either truncation of the PAX6 protein or conservative amino acid changes in the paired domain. We also detected two intronic non-pathogenic variations, IVS9-12C>T and IVS2+9G>A, that had been previously reported. Because the latter variation was considered potentially pathogenic, it was analyzed in 103 healthy Mexican newborns where we found an allelic frequency of 0.1116 for the A allele.
This study adds four novel mutations to the worldwide PAX6 mutational spectrum, and reaffirms the finding that c.969C>T is one of the three more frequent causal mutations in aniridia cases. It also provides evidence that IVS2+9G>A is an intronic change without pathogenic effect.
Molecular vision 01/2008; 14:1650-8. · 2.20 Impact Factor
