Primary immunodeficiencies (PIDs) are genetic disorders that predispose to frequent and severe infections, autoimmunity and
cancer. The expanded life span of such patients increases the overall risk ...for developing cancer, which is now estimated at
4-25% . The type of malignancy depends on the primary immunodeficiency, the age of the patient and possible viral infection,
suggesting that different pathogenetic mechanisms are implicated in each case. Non-Hodgkin's lymphomas predominate, accounting
for 60% of cases. The PIDs known to be associated with increased incidence of malignancy are: common variable immunodeficiency,
IgA deficiency and DNA repair disorders. During recent years other types have also been included, such as severe combined
immunodeficiency (SCID) and Wiskott Aldrich syndrome (WAS).
The ATM Gene and Ataxia Telangiectasia MAVROU, Ariadni; TSANGARIS, George Th; ROMA, Eleftheria ...
Anticancer research,
01/2008, Letnik:
28, Številka:
1B
Journal Article
Recenzirano
Ataxia telangiectasia (AT) is a rare neurodegenerative, autosomal recessive disorder characterized by chromosome instability,
radiosensitivity, immunodeficiency and a predisposition for cancer. ...Epidemiological studies have shown that AT heterozygotes
have a predisposition for cancer, especially for breast cancer in women. The disease is caused by mutations in the ATM gene,
leading to total loss of the ATM protein, which normally recognizes DNA damage, activates the DNA repair machinery and the
cell cycle check points in order to minimize the risk of genetic damage. This review summarizes the clinical features of AT
and the natural history of the disease and puts recent molecular advances into the context of the cellular and clinical phenotype.
46,XX male sex reversal syndrome is a rare genetic cause of male infertility. We report on two new cases of this syndrome in men presenting with hypogonadism and infertility. Cytogenetic and ...molecular analysis was performed in both patients. An extensive review of the literature for 46,XX male sex reversal syndrome cases related to infertility was also performed to fully characterise this syndrome. Genetic analyses showed translocation of the SRY on Xp chromosome and complete absence of all Azoospermia factor (AZF) genetic regions. All patients included in the review presented hypergonadotropic hypogonadism. Small testes were the most common clinical characteristic present in 90.2% of the patients, followed by small penis (31.8%), gynecomastia (26.8%) and poor hair distribution (15.4%). The presence of the SRY was identified in 130/154 (84.4%) patients: in 98.5% of cases, it was translocated on the Xp chromosome and in 1.5% on an autosome. All patients were azoospermic, due to the lack of AZF genetic regions. Males with normal phenotype and primary hypogonadism should be properly evaluated by the physicians and must be referred for cytogenetic and molecular analysis to exclude or confirm 46,XX male sex reversal syndrome. More cases of this syndrome with SRY translocated on an autosome are needed to identify if these patients have different characteristics than those with SRY translocated on Xp chromosome. Whole genome analysis of these patients is required to elucidate the genetic differences which are responsible for the phenotypic variability of the syndrome.
Sotos syndrome is characterized by tall stature, advanced bone age, typical facial abnormalities, and developmental delay. The associated gene is NSD1 . The study involved 22 patients who fulfilled ...the clinical criteria. Phenotypic characteristics, central nervous system findings, and cardiovascular and urinary tract abnormalities were evaluated. Meta-analysis on the incidence of cardinal clinical manifestations from the literature was also performed. Macrocephaly was present in all patients. Advanced bone age was noted in 14 of 22 patients (63%), and its incidence presented significant statistical difference in the meta-analysis of previous studies. Some patients had serious clinical manifestations, such as congenital heart defects, dysplastic kidneys, psychosis, and leukemia. Clinical and laboratory examinations should be performed to prevent and manage any unusual medical aspect of the syndrome. Facial gestalt and macrocephaly, rather than advanced bone age, are the strongest indications for clinical diagnosis.
Advances in technologies associated with mass spectrometry-based proteomic techniques have added a new dimension to the field of biomedical research. Most of the existing research on human gestation ...has focused on the application of these high-throughput methodologies in the study of amniotic fluid. In cases of fetal aneuploidies, the use of proteomic platforms has contributed to the identification of relevant protein biomarkers that could potentially change early diagnosis and treatment. The current article focuses on studies of normal amniotic fluid using proteomic technologies and describes alterations noted in the amniotic fluid proteome in the presence of fetal aneuploidies.
Objective To establish the diagnosis of complete androgen insensitivity syndrome (CAIS) in two patients with characteristic clinical and hormonal findings, relative family history in one of them, and ...unusual Müllerian remnants in the other. Design Case report. Setting Research laboratory in the Department of Medical Genetics at a university children's hospital. Patient(s) Two patients with 46,XY sex reversal and two maternal aunts of the first patient with the same clinical condition were tested. Intervention(s) Bilateral gonadectomy was performed on both patients. Main Outcome Measure(s) Genetic counseling, cancer prophylaxis, hormone substitution therapy. Result(s) Molecular analysis revealed two novel mutations, a frameshift familial (c.2494delA) in patient 1 and a missense sporadic (c.T3004C) in patient 2. The c.2494delA mutation was also detected in two of the three affected maternal aunts of patient 1. Patient 2 presents an unusual persistence of Müllerian structures. Conclusion(s) Genetic counseling of potential women carriers of androgen receptor (AR) mutations is crucial for the early diagnosis of the affected offspring. The presence of Müllerian remnants, although rare, should not exclude the diagnosis of CAIS. Both identified mutations are novel and provide further evidence for the correlation between specific AR mutations and phenotype.
MicroRNAs (miRNAs) constitute a highly conserved class of small non-coding RNAs, involved in post-transcriptional regulation processes by modifying the expression of specific mRNAs. During placental ...development, cell differentiation, adhesion, migration, apoptosis and angiogenesis are regulated by specific miRNAs and aberrant expression has been associated with the pathogenesis of pregnancy-related complications. Recent studies focusing on placental and maternal peripheral blood miRNA profiling showed different expression between normal and complicated pregnancies, providing valuable information about the pathophysiological role of miRNAs and identifying potential biomarkers for monitoring pregnancy complications. This review summarizes the current knowledge in the field and presents the possible use of miRNAs as biomarkers for early detection and monitoring of these complications.
X chromosome architecture and integrity are essential for normal ovarian function. Both numerical and structural X chromosome abnormalities play an important role in female infertility. This study ...aimed to determine the types and frequency of X chromosome aberrations detected in women referred for cytogenetic investigation due to reproductive problems.
2,936 women (average age: 37.5 years) were enrolled in the present study. Peripheral blood karyotyping was performed by conventional cytogenetic techniques. For each woman, 20 G-banded metaphases were studied and in case of suspected mosaicism, analysis was extended to 100 metaphases.
2,588/2,936 (88.15%) of women had a normal karyotype (46,XX), while 348/2,936 (11.85%) had an abnormal one. Thirty-two women (1.09%) carried autosomal chromosome abnormalities and 316 (10.76%) had X chromosome rearrangements. In 311/2,936 women (10.59%), X chromosome numerical aberrations were detected (low-level mosaicism), and in 5/2,936 cases (0.17%), X structural abnormalities (two with pericentric inversion, one with Xq deletion and two 45,X mosaics, one with an Xp deletion cell line and the other with isochromosome Xq cell line). Low-level X mosaicism was a common finding in women >35 years as compared to younger ones (92.93% vs. 7.07%), a finding consistent with loss of chromosome X with aging. Other X chromosome abnormalities were detected in younger women (32.3 ± 4.13 vs. 41.04 ± 4.5 years). The mean age of women with Turner-like phenotype was 28.75 ± 6.6 years.
The study confirms that the incidence of X chromosome abnormalities is increased in women with fertility problems and that karyotype is the gold standard for their identification. Genetic counseling is recommended in these cases to provide information concerning available treatment and fertility options.
Proteomic analysis combining two-dimentional electrophoresis (2DE) and mass spectrometry (MS) has the potential for a wide
range of applications in biological and medical sciences, as protein ...screening in tissues obtained from healthy and diseased
conditions can determine drug targets and diagnostic markers. Conventionally, amniotic fluid (AF) samples are routinely used
for prenatal diagnosis of a wide range of fetal abnormalities. Proteomics have already been applied in the analysis of tissues
from fetuses with Down's syndrome, in order to detect differences in their protein profile as compared to the normal profiles
and to determine possible diagnostic tools. A detailed protein 2DE for the normal human AF has not been reported. In the present
study, the 2D protein database of the normal human AF supernatant (AFS) was constructed. Ten AFS samples from women carrying
normal fetuses were analysed by 2DE. A mean of 412 spots per gel were analyzed and protein identification was carried out
by MALDI-MS and MALDI-MS-MS. A 2D protein map comprising of 136 different gene products was constructed. The majority of the
identified proteins are regulatory proteins, enzymes, secreted proteins, carriers and immunoglobulins. Twelve hypothetical
proteins were also included. The normal AFS proteome map is a valuable tool for the study of aberrant protein expression and
the search for proteins as possible markers for the prediction of abnormal fetuses.
To determine the miRNA expression profile in placentas complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies.
Sixteen placentas from women with PE, 11 with early onset PE ...(EOPE) and 5 with late onset PE (LOPE), as well as 8 placentas from uncomplicated pregnancies were analyzed using miRNA microarrays. For statistical analyses the MATLAB® simulation environment was applied. The over-expression of miR-518a-5p was verified using Quantitative Real-Time Polymerase Chain Reaction.
Forty four miRNAs were found dysregulated in PE complicated placentas. Statistical analysis revealed that miR-431, miR-518a-5p and miR-124* were over-expressed in EOPE complicated placentas as compared to controls, whereas miR-544 and miR-3942 were down-regulated in EOPE. When comparing the miRNA expression profile in cases with PE and PE-growth restricted fetuses (FGR), miR-431 and miR-518a-5p were found over-expressed in pregnancies complicated by FGR.
Since specific miRNAs can differentiate EOPE and LOPE from uncomplicated placentas, they may be considered as putative PE-specific biomarkers. MiR-518a-5p emerged as a potential diagnostic indicator for EOPE cases as well as for PE-FGR complicated placentas, indicating a potential link to the severity of the disease.
•We aimed to identify placental miRNAs for PE.•Samples were analyzed by microarray and following by bioinformatics and statistics and further validated with qRT-PCR.•The results obtained showed that specific miRNAs can differentiate EOPE and LOPE.
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