Annales de Génétique最新文献

Peptide nucleic acids (PNAs) are synthetic homologs of nucleic acids in which the phosphate–sugar polynucleotide backbone is replaced by a flexible pseudo-peptide polymer to which the nucleobases are linked. This structure gives PNAs the capacity to hybridize with high affinity and specificity to complementary sequences of DNA and RNA, and also confers remarkable resistance to DNAses and proteinases. The unique physico-chemical characteristics of PNAs have led to the development of a wide range of biological assays. Several exciting new applications of PNA technology have been published recently in genetics and cytogenetics. Also, PNA-based hybridization technology is developing rapidly within the field of in situ fluorescence hybridization, pointing out the great potential of PNA probes for chromosomal investigations.

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.

The objective of this study was to evaluate the contribution of ultrasound scanning to the prenatal detection of trisomy 21 in a large unselected European population. Data from 19 congenital malformation registers in 11 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient. Routine serum screening was offered in four of the 11 countries and routine screening on the basis of maternal age amniocentesis in all. The results show that overall 53% of cases of trisomy 21 were detected prenatally with a range from 3% in Lithuania to 88% in Paris. Ninety-eight percent of women whose babies were diagnosed before 24 weeks gestation chose to terminate the pregnancy. Centres/countries that offer serum screening do not have a significantly higher detection rate of trisomy 21 when compared to those that offer maternal age amniocentesis and anomaly scanning only. Fifty percent of trisomy 21 cases were born to women aged 35 years or more. In conclusions, second trimester ultrasound plays an important role in the prenatal diagnosis of trisomy 21. Of those cases prenatally diagnosed, 64% of cases in women <35 years and 36% of those in women ≥35 years were detected because of an ultrasound finding. Ultrasound soft markers accounted for 84% of the scan diagnoses. There is evidence of increasing maternal age across Europe with 50% of cases of trisomy 21 born to women aged 35 years or more.

This report presents a case with partial trisomy 18q resulting from de novo unbalanced translocation of chromosomes 15 and 18 displaying the features of pure trisomy. This is the first reported case with partial trisomy 18q due to unbalanced translocation between chromosomes 15 and 18. Clinical findings of our case have been compared with the reported cases’ had partial trisomy 18q and the importance to recognize the cases with chromosome abnormalities to give genetic counseling and prenatal diagnosis for subsequent pregnancies has emphasized.

We report on a 5-year-old Tunisian boy with particular dysmorphic features and mild mental retardation limited in delayed and poor language acquisition. Cytogenetic analysis using RHG banding and FISH using whole chromosome four painting probe showed a partial duplication in the long arm of chromosome four. Locus specific probes and CGH confirmed the presence of a ‘‘pure’’ partial trisomy 4q due to de novo direct tandem dup(4)(q25q34). Comparative analysis of our case with those published previously, suggests that region 4q31–q33 may be involved in the development of the 4q characteristic dysmorphic features and the distal band 4q35 may be involved in the development of microcephaly and severe mental and growth retardation.

Transforming growth factor beta (TGFβ) is a secreted protein present in the circulation and is a critical regulator of the body's immune system. TGFβ is believed to control several components of the immune system and inhibit autoimmune reactions. Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are prototypical human autoimmune diseases characterized by the circulating autoantibodies directed against nuclear antigens and immune complex deposition in various tissues leading to target organ inflammation and damage. Although the etiology of SLE is unknown, it has been observed that patients with SLE have lower levels of circulating TGFβ than healthy individuals. In addition, mice lacking the TGFβ1 gene develop a severe autoimmune disease that has features of both SS and SLE. Polymorphisms in the TGFβ1 gene may alter the mRNA expression levels and influence the plasma protein concentration. Of the known TGFβ 1 polymorphisms, only the C-509T polymorphism in the promoter region has been shown to be significantly associated with the plasma concentrations of TGFβ 1. In this study, we have conducted a blinded study to determine if the -509 TGFβ1 gene polymorphism is associated with SS or SLE. Genomic PCR and RFLP analysis of a 441 bp sequence encompassing the –509 polymorphism of the TGFβ gene indicated that there were no statistically significant clinical correlations.

The studies of the HFE mutations: H63D and C282Y in North African populations have revealed the extreme rarity or even the absence of the C282Y mutation. We have examined 1140 chromosomes (570 Tunisian people) for the presence of the two HFE mutations by PCR-RFLP analysis. We have found that the allele frequencies are, respectively, 15.17% (±2.1%) for the H63D and 0.09% (±0.17%) for the C282Y. These results are consistent with the worldwide spread of the H63D mutation and the north European restriction of the C282Y. This study will be completed by determining whether homozygote trait for H63D and associated risk factors (ß thalassémia) can lead to iron overload in Tunisia.