Complex X chromosome rearrangement associated with multiorgan autoimmunity.

BACKGROUND: Turner syndrome, a congenital condition that affects 1/2,500 births, results from absence or structural alteration of the second sex chromosome. Turner syndrome is usually associated with short stature, gonadal dysgenesis and variable dysmorphic features. The classical 45,X karyotype accounts approximately for half of all patients, the remainder exhibit mosaicism or structural abnormalities of the X chromosome. However, complex intra-X chromosomal rearrangements involving more than three breakpoints are extremely rare. RESULTS: We present a unique case of a novel complex X chromosome rearrangement in a young female patient presenting successively a wide range of autoimmune diseases including insulin dependent diabetes mellitus, Hashimoto's thyroiditis, celiac disease, anaemia perniciosa, possible inner ear disease and severe hair loss. For the genetic evaluation, conventional cytogenetic analysis and FISH with different X specific probes were initially performed. The complexity of these results and the variety of autoimmune problems of the patient prompted us to identify the exact composition and breakpoints of the rearranged X as well as methylation status of the X chromosomes. The high resolution array-CGH (assembly GRCh37/hg19) detected single copy for the whole chromosome X short arm. Two different sized segments of Xq arm were present in three copies: one large size of 80,3 Mb from Xq11.1 to Xq27.3 region and another smaller (11,1 Mb) from Xq27.3 to Xq28 region. An 1,6 Mb Xq27.3 region of the long arm was present in two copies. Southern blot analysis identified a skewed X inactivation with ≈ 70:30 % ratios of methylated/unmethylated fragments. The G-band and FISH patterns of the rearranged X suggested the aspect of a restructured i(Xq) chromosome which was shattered and fortuitously repaired. The X-STR genotype analysis of the family detected that the patient inherited intact maternal X chromosome and a rearranged paternal X chromosome. The multiple Xq breakages and fusions as well as inverted duplication would have been expected to cause a severe Turner phenotype. However, the patient lacks many of the classic somatic features of Turner syndrome, instead she presented multiorgan autoimmune diseases. CONCLUSIONS: The clinical data of the presented patient suggest that fragmentation of the i(Xq) chromosome elevates the risk of autoimmune diseases.

Increased circulating heat shock protein 70 (HSPA1A) levels in gestational diabetes mellitus: a pilot study.

Recent data indicate that serum Hsp70 (HSPA1A) levels are increased in type 1 and 2 diabetes mellitus. However, there is no report in the literature on circulating Hsp70 levels in gestational diabetes mellitus. In this pilot study, we measured serum Hsp70 levels in 11 pregnant women with pregestational diabetes, 38 women with gestational diabetes, and 40 healthy pregnant women with ELISA. Plasma glucose levels, serum insulin concentrations, HbA1c values, and the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were also determined. According to our results, serum Hsp70 concentrations were significantly higher in women with pregestational and gestational diabetes mellitus than in healthy pregnant women. In addition, pregestational diabetic women had significantly higher Hsp70 levels than those with gestational diabetes. Furthermore, in the group of women with gestational diabetes mellitus, serum Hsp70 levels showed a significant positive correlation with HbA1c values. However, there was no other relationship between clinical features and metabolic parameters of the study subjects and their serum Hsp70 levels in either study group. In conclusion, we demonstrated for the first time in the literature that serum Hsp70 levels are increased and correlate with HbA1c values in women with gestational diabetes mellitus. Nevertheless, further studies are needed to determine whether circulating Hsp70 plays a causative role in the pathogenesis of gestational diabetes or elevated serum Hsp70 levels are only consequences of the disease.

Incidence and causes of maternal thrombocytopenia in triplet gestation.

OBJECTIVE: To determine the incidence, clinical significance and causes of maternal thrombocytopenia in triplet gestations. STUDY DESIGN: The study population consisted of 150 patients with triplet gestation that delivered at our department between 1990 and 2008. Thrombocytopenia was defined as a platelet count <150,000/µL. Patients were classified on the basis of the lowest recorded platelet count observed during pregnancy. RESULTS: A low platelet count was observed during the triplet gestation in 36 cases (24.0%), and after delivery in another 19 cases (12.7%). Thrombocytopenia was mild, moderate, and severe in 75% (27/36), 16.7% (6/36), and 8.3% (3/36) of the cases, respectively. During pregnancy, thrombocytopenia was associated with pregnancy-induced hypertension in 25.0% (9/36) of patients, while gestational thrombocytopenia was diagnosed in 72.2% of the cases (26/36). The mean platelet count showed a strong negative correlation with gestational age (r=-0.953, P<0.001), and at 36 weeks approached the limit of thrombocytopenia. CONCLUSIONS: Thrombocytopenia occurs more frequently in triplet gestations than in the general pregnant population, and the rate of moderate and severe forms is higher. The distribution of causes is comparable to that of the general pregnant population. The average platelet count in triplet gestations decreases with gestational age.

Serum selenium concentrations correlate significantly with inflammatory biomarker high-sensitive CRP levels in Hungarian gestational diabetic and healthy pregnant women at mid-pregnancy.

Selenium is an essential trace element and a component of various enzymes with antioxidant functions. High-sensitive C-reactive protein (hsCRP) is an early indicator of increased lipid peroxidation. The serum selenium concentration, lipid parameters, and hsCRP values of gestational diabetic pregnant women (GD), control pregnant women (CP), and healthy nonpregnant controls (HC) were compared. Blood was taken between the 24th and the 28th week of pregnancy when the oral glucose tolerance test was performed. Selenium concentration was determined by atomic absorption spectrometry after hydride generation. HsCRP was measured by immunturbidimetry. HC had significantly higher serum selenium concentrations than GD and CP women (HC = 77.4 +/- 14.82, GD = 51.7 +/- 11.62, and CP = 40.5 +/- 8.03 microg/l, respectively). HsCRP values of both GD and nondiabetic pregnant women were significantly higher compared to controls. Significant negative correlations were found between serum selenium and total cholesterol, low-density lipoprotein cholesterol, and hsCRP values indicating that low selenium levels are associated with increased lipid peroxidation. Serum selenium concentrations of Hungarian pregnant women are low compared to internationally published data.