Phenotype variability in a large Spanish family with Alport syndrome associated with novel mutations in COL4A3 gene.

BACKGROUND: Alport syndrome is an inherited renal disorder characterized by glomerular basement membrane lesions with hematuria, proteinuria and frequent hearing defects and ocular abnormalities. The disease is associated with mutations in genes encoding α3, α4, or α5 chains of type IV collagen, namely COL4A3 and COL4A4 in chromosome 2 and COL4A5 in chromosome X. In contrast to the well-known X-linked and autosomal recessive phenotypes, there is very little information about the autosomal dominant. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. METHODS: We investigated a Spanish family with variable phenotype of autosomal dominant Alport syndrome using clinical, histological, and genetic analysis. RESULTS: Mutational analysis of COL4A3 and COL4A4 genes showed a novel heterozygous mutation (c. 998G > A; p.G333E) in exon 18 of the COL4A3 gene. Among relatives carrying the novel mutation, the clinical phenotype was variable. Two additional COL4A3 mutations were found, a Pro-Leu substitution in exon 48 (p.P1461L) and a Ser-Cys substitution in exon 49 (p.S1492C), non-pathogenics alone. CONCLUSION: Carriers of p.G333E and p.P1461L or p.S1492C mutations in COL4A3 gene appear to be more severely affected than carriers of only p.G333E mutation, and the clinical findings has an earlier onset. In this way, we could speculate on a synergistic effect of compound heterozygosity that could explain the different phenotype observed in this family.

[Retrotrigonal bladder lymphoma]. / Linfoma vesical de localización retrotrigonal.

Presentation of one case of vesical involvement due to lymphoma in an 82-year old female which presented as a micturition syndrome, abdominal mass and later picture of obstructive uropathy with acute renal function impairment. Diagnosis was achieved by ultrasound and abdominal CAT, cystoscopy with of vesical biopsy, transvaginal mass biopsy and immunohistochemical techniques. The difficulties of a correct differential diagnosis with other vesical neoplasias as well as the need to differentiate primary from systemic vesical lymphoma were discussed, not only because of the separate prognosis but also for the different therapeutical approaches.

[Hormonal changes in fertile women with quiescent systemic lupus erythematosus]. / Alteraciones hormonales en mujeres fértiles con lupus eritematoso sistémico quiescente.

The hypophyseal-adrenal-ovarian axis was studied in 29 women of childbearing age with systemic lupus erythematosus, as well as in a control group of 14 healthy women. Hormonal levels were measured on days 7th and 21st of menstrual cycle. Women with systemic lupus erythematosus had not significatively lower testosterone levels, but progesterone and 17-alfa-hydroxiprogesterone levels were markedly lower when compared to controls. These facts suggest a decrease in progesterone levels, which could act as a predisposing factor for lupic disease.