Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

[Endocardial ablation of substrate of postinfarction ventricular tachycardia during sinus rhythm]. / Ablación endocárdica del sustrato de taquicardia ventricular postinfarto durante ritmo sinusal.

OBJECTIVE: Radiofrequency ablation of ventricular tachycardia requires good tachycardia tolerance during mapping and entrainment, and this limits its application. We present our initial experience with ventricular tachycardia ablation during sinus rhythm in 7 patients with previous inferior myocardial infarction. METHODS: Seven men, 56-70 years old (mean +/- SD, 65 +/- 4.5) were included in the study. Ventricular tachycardia was unstable in 6 and in 1 it was induced non-sustained. The scar was localized by recording low-voltage, fragmented electrograms (< 2 mV). Ventricular tachycardia "exit" was localized by pace-mapping in sinus rhythm. Radiofrequency lines were made radially, point by point, from normal to scarred tissue. One of the lines crossed the exit area. The objective was to achieve non-inducibility. RESULTS: Sustained clinical ventricular tachycardia was induced in 6 and non-sustained in 1. Two-four lines were performed per patient with 11-28 (21 +/- 5.4) radio frequency applications. The procedure duration was of 130-280 min (230 +/- 61) and being 49-75 min (63 +/- 7.9) for fluoroscopy. There were no complications. Clinical ventricular tachycardia became non-inducible in 6, although in 4 a rapid (cycle < or = 250 ms), non-clinical ventricular tachycardia remained inducible. Defibrillators were implanted in the patient remaining inducible for clinical ventricular tachycardia and another with > 60 tachycardia episodes the previous week. During 3-22 months (13.8 +/- 5.9) of follow-up, 1 patient died of heart failure at 20 months and another received 3 defibrillator shocks for VT at 13 months. There were no other episodes of ventricular tachycardia, syncope or sudden death. CONCLUSIONS: This preliminary experience suggests that radiofrequency ablation of post-infarction ventricular tachycardia substrate is possible during sinus rhythm, suggesting that radiofrequency ablation may be applicable in a large proportion of patients with post-infarction sustained ventricular tachycardia.

[Perforated duodenal ulcer in children]. / Ulcus duodenal perforado en la infancia.

We face a case of duodenal ulcer perforation a nine year old child who's diagnosis was not detected before operating. This is an unusual case and it is not normally observed in the differential diagnosis of the acute abdominal pain in the infancy. The lack of the radiological signs of perforation contributed to the diagnosis mistake before operating.

Cuerpo extraño intramiocárdico sin consecuencias / Asymptomatic intramyocardial foreign body

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Factor V Leiden y trombosis de arteria central de retina / Factor V Leiden and retinal central artery thrombosis

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Neurotoxicidad por fenitoína / Phenitoin neurotoxicity

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