Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases.

The mode of inheritance of Alport syndrome (ATS) has long been controversial. In 1927, the disease was hypothesized as a dominant condition in which males were more severely affected than females. In 1990, it was considered an X-linked (XL) semidominant condition, due to COL4A5 mutations. Later on, a rare autosomal recessive (AR) form due to COL4A3/COL4A4 mutations was identified. An autosomal dominant (AD) form was testified more recently by the description of some large pedigrees but the real existence of this form is still questioned by many and its exact prevalence is unknown. The introduction of next generation sequencing (NGS) allowed us to perform an unbiased simultaneous COL4A3-COL4A4-COL4A5 analysis in 87 Italian families (273 individuals) with clinical suspicion of ATS. In 48 of them (55%), a mutation in one of the three genes was identified: the inheritance was XL semidominant in 65%, recessive in 4% and most interestingly AD in 31% (15 families). The AD form must therefore be seriously taken into account in all pedigrees with affected individuals in each generation. Furthermore, a high frequency of mutations (>50%) was shown in patients with only 1 or 2 clinical criteria, suggesting NGS as first-level analysis in cases with a clinical suspicion of ATS.

Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype-genotype correlations in Beckwith-Wiedemann syndrome.

BACKGROUND: The phenotypic variability in Beckwith-Wiedemann syndrome (BWS) reflects the genetic heterogeneity of the mechanism which by default leads to the deregulation of genes located at 11p15.5. Genotype-phenotype correlation studies have demonstrated an association between omphalocoele and CDKN1C/p57 mutations or hypermethylation. Paternal uniparental disomy 11 (pUPD11) has been described only in the mosaic condition with both uniparental and biparental cell lines, and no association with omphalocoele has been pointed out. METHODS: Two cases are presented here, in which a paternal segmental UPD11 was detected by molecular investigation of amniotic fluid cell cultures after the presence of apparently isolated omphalocoele was revealed in the fetuses by ultrasound scan. Further studies were performed on additional autoptic feto-placental tissues to characterise the distribution of the uniparental cell line and to unmask any biparental lineage in order to document in more detail the as yet unreported association between omphalocoele and pUPD11. RESULTS: Results on the UPD distribution profile showed that the abdominal organs have a predominant uniparental constitution. This condition could mimic the effect of CDKN1C/p57 inactivation, causing the omphalocoele. CONCLUSION: New genotype-phenotype correlations emerge from the investigated cases, suggesting that molecular analysis be extended to all cases with fetal omphalocoele in order to establish the incidence of pUPD11 in complete BWS and in monosymptomatic/mild forms.

[Vaginal intraepithelial neoplasia and human papillomavirus infection: a report of 75 cases]. / La neoplasia intraepiteliale vaginale e l'infezione da virus del papilloma umano. Un resoconto di 75 casi.

AIM: Vaginal intraepithelial neoplasia (VaIN) is an uncommon and poorly understood disease. Risk factors other than human papillomavirus (HPV) infection could be linked to the onset and evolution of some VaIN. METHODS: In this paper, the results achieved from the analysis of 75 patients with VaIN are reported. From these cases, women with HIV, previous hysterectomy, autoimmune diseases and radio- and chemotherapy have been excluded. Thus, most of these selected cases should be linked to the HPV infection. They have been examined after a distinction between grade and association with coilocytosis. VaIN preferential localization, mean age of patients and manifestation pattern after vaginal colposcopy have then been examined. RESULTS: Although the population size cannot allow evidences, it seems that VaIN with coilocytosis and VaIN I without coilocytosis have preferential localization in the upper third of the vagina. It does not appear that mean age of patients for each grade of VaIN differs significativly, both associated and not associated with coilocytosis. Finally, after vaginal colposcopy, the pattern of VaIN for each grade is absolutely not typical, and it seems that white thin epithelium or negative Lugol area are usually the manifestation of high grades of VaIN too. CONCLUSIONS: These results, if confirmed, could mean that VaIN due to HPV may have a different natural history relating to the site of localization in the vagina and, moreover, that also VaIN of high grade could appear with an innocent vaginal pattern.

[A natural alternative to menopausal hormone replacement therapy. Phytoestrogens]. / Un'alternativa naturale alla terapia ormonale sostitutiva in menopausa.. I fitoestrogeni.

Phytoestrogens are non-steroidal plant molecules whose structure differs from gonadal hormones, but with an estrogen-type bioactivity: they are capable of interacting with estrogen receptors, showing both agonist and antagonist methods of action. The beneficial effects of various classes of phytoestrogens present in nature are now known, but the main isoflavone present in soya, genistein, appears to be particularly effective. Interest in this substance is concentrated in particular on its therapeutic role in menopause. This paper is a review of the main studies published to date on the efficacy of phytoestrogens in reducing the symptoms of menopause. A diet rich in isoflavones is associated with a reduced incidence of vasomotor episodes; the average supplement of genistein is approximately 50 mg/day. After supplementing the diet with phytoestrogens, studies show a reduction in total cholesterol and LDL fraction. This is accompanied by an increase in BMD (Bone mineral density) after taking 90 mg of isoflavones for 6 months. Isoflavones may reduce the risk of developing breast cancer. The data examined confirm the excellent clinical efficacy of supplementing the diet with soy extracts, particularly genistein which is indicated to alleviate both the short-term symptoms of menopause and the long-term effects, although the latter finding requires further subsantiation.