A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management

Abstract

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS.

Methods: Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed.

Results: During hormonal evaluation elevated serum concentration of FSH and LH and decreased serum concentration of estradiol were measured. The genetic testing revealed translocation 7;14 (t(7;14)) and inversion 7 in 22% of examined cells which confirmed the initial hypothesis of NBS. The diagnosis was finally verified by identifying a Slavic founder mutation, c.657_661del5, on both allels of the NBN gene. Furthermore, hormonal serum evaluation conducted after four weeks allowed the patient to be diagnosed with premature ovarian insufficiency (POI) suspected earlier on the grounds of preliminary examinations (ultrasound imaging and laboratory tests).

Conclusions: Chromosomal instability resulting from a mutation present in Nijmegen breakage syndrome patients might be a causative factor of premature ovarian insufficiency. Therefore, females diagnosed with NBS should undergo additional diagnostic procedures in order to determine further management and treatment.     

Effects of prenatal gamma-irradiation on postnatal astrogliogenesis in the hippocampal formation of rat

Female Wistar rats were exposed to a single 1.0 Gy dose of gamma radiation on gestational days 13, 15, 17 or 19 (E13, E15, E17 and E19, respectively). Their 8- and 16-day old male offsprings were injected with ³H-thymidine and sacrificed 4 h after the injection. Brain sections were immunostained for S100β protein and subjected to autoradiography. Thereafter, the dorsal part of the hippocampal formation was examined microscopically and numbers and locations of proliferating astrocytes were recorded. Following prenatal irradiation, the intensity of astrocyte proliferation was considerably reduced, especially in the region of dentate gyrus. The reduction showed regular trend of changes being much stronger in brains irradiated on E19 than in those irradiated on E13. The changes, therefore, were related to the stage of brain development at which the irradiation was performed. A possible role of neuronal regulatory influence on the postnatal development of glial cells was discussed.     

Effect of ivabradine on cardiac arrhythmias: Antiarrhythmic or proarrhythmic?

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Mannan-binding lectin-2 (MBL2) gene polymorphisms in prenatal and perinatal cytomegalovirus infections

Cytomegalovirus (CMV) is the leading cause of congenital infections among neonates. About 10% of newborns with such an infection have clinical symptoms at birth and about 1% of infected fetuses die due to developmental malformations. Mannan-binding lectin (MBL) is considered to be an important factor in innate immunity. Its deficiency is believed to predispose to various (including viral) infections. The aim of this study was to investigate the possible role of MBL2 gene polymorphisms in prenatal and perinatal CMV infections. The frequencies of MBL2 gene exon 1 mutations as well as MBL deficiency-associated variants (LXPA/O+O/O) among newborns with confirmed cytomegalovirus infection were not significantly lower than among non-infected individuals. The distribution of MBL2 haplotypes was similar between the groups studied. These data suggest MBL does not have a major influence on susceptibility to prenatal or perinatal CMV infections.     

Sialylation of intracellular proteins of thyroid lesions

Enhanced sialylation represents one of the most frequently occurring alterations of the sugar chain structure in various cancers. However, up to now, sialylation of intracellular proteins of thyroid carcinomas has never been investigated. The aim of this study was comparative analysis of cytoplasmic and nuclear sialoglycoproteins isolated from thyroid benign and malignant tumors as well as non-neoplastic lesions. The sialylation level and types of sialic acid linkages were analysed by lectin blotting and enzyme linked lectino-solid-phase assay (ELLSA) using Sambucus nigra (SNA) and Maakia amurensis (MAA) agglutinins. The presence of alpha2,6 and alpha2,3 linked sialic acid residues was detected in all types of thyroid lesion specimens but there were some differences in the banding and intensity patterns. Analysis of SNA and MAA binding by ELLSA method showed that in the majority of cancer samples the level of sialic acid residues was lower than in non-neoplastic lesions and adenomas. Our present results suggest that decrease in sialylation rather than increase is a characteristic feature of malignant transformation in the thyroid.     

Delineation variation of lymph node stations for treatment planning in lung cancer radiotherapy.

PURPOSE: To assess the variability among clinicians in the delineation of mediastinal and hilar lymph node stations (LNS) according to the published recommendations in the treatment planning of elective nodal irradiation for lung cancer. METHODS: Nine observers delineated on axial CT scans of five cases the LNS according to the guidelines of the published Atlas. Next, the Volumes of Consensus (VC)--fitting strictly the guidelines--for each LNS and case were collectively defined. Volume of Intersection (VI) as the overlap of the Delineated Volume (DV) for each LNS, case and observer with respective VC was computed. The Concordance Index (CI) for respective LNS and observers was defined as "VI/VC x 100%". The Discordance Index (DI) for respective LNS and observers was defined as "(1-VI/VD) x 100%". RESULTS: Mean values of CI and DI for all observers were 69% and 36%, respectively. For five radiation oncologists who used to work as a team the ways of delineation were similar. The poorest reproducibility was shown for LNS 5, 7, 10R, and 10L. CONCLUSIONS: Although detailed guidelines are used there is still substantial room for improvement. More training in the use of the Atlas is recommended.