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The X-linked Alport syndrome (ATS) is caused by mutations in COL4A5 and exhibits a widely variable expression. Usually ATS is heralded with continuous microhematuria which rapidly progresses to proteinuria, hypertension and chronic or end-stage renal disease (ESRD) by adolescence, frequently accompanied by sensorineural deafness and ocular complications. Milder forms of ATS also exist. We studied 42 patients (19M, 23F) of nine Hellenic families suspected clinically of X-linked ATS who presented with marked phenotypic heterogeneity. We identified mutations in COL4A5 in six families. Two males with nonsense mutation E228X reached ESRD by ages 14 and 18. Frameshift mutation 2946delT followed the same course with early onset renal involvement and deafness. However, two males with the milder missense mutation G624D, reached ESRD after 39 years and one patient showed thin basement membrane nephropathy (TBMN). Another 5/8 affected males with missense mutation P628L also developed ESRD between 30 and 57 years, while three exhibit only mild chronic renal failure (CRF). The data support previous findings that certain mutations are associated with milder phenotypes and confirm that mutation G624D may be expressed as TBMN with familial hematuria. Similar conclusions apply for missense mutation P628L. Interestingly, mutations G624D and P628L are near the 12th natural interruption of COL4A5 triple helical domain, which may explain the milder phenotype. © 2011 John Wiley & Sons A/S. 81 240 248

Aims: To investigate clinically and genetically all the distal renal tubular acidosis (dRTA) cases in Cyprus, to study one more family from Greece and to perform the first dRTA prenatal diagnosis. We also tried to find any association with sensorineural hearing loss (SNHL) onset and particular mutations. Methods: Nine dRTA families from Cyprus and one from Greece were analyzed for mutations in ATP6V1B1 gene by DNA resequencing and PCR-RFLPs. Clinical diagnosis was performed by standard criteria. Prenatal diagnosis was performed for one Cypriot family. Results: Results show that 7/9 dRTA cases in Cyprus are caused by 229+1G>T and R157C founder mutations in ATP6V1B1 gene. 229+1G>T mutation was estimated to be older than 400 years. No genotype- phenotype correlation was found with SNHL. A known (L81P) and a novel mutation (912delT) were found in the Greek family. Prenatal diagnosis was performed for one Cypriot family, after parents' demand, showing that the embryo was a heterozygous carrier. Conclusion: Existence of only two ATP6V1B1 mutations in the Cypriot population is a diagnostic advantage. The age of onset of SNHL varies in our patients and probably is not related to ATP6V1B1 genotypes. Effective therapy for most of the syndrome symptoms is not satisfactory for some parents who choose prenatal diagnosis to ensure their child's health. Copyright © 2010 S. Karger AG, Basel. 117 c206 c212 Cited By :6

Sirs,The idiopathic nephrotic syndrome is a common clinico-pathological entity characterized by massive proteinuria,hypoalbuminaemia, hyperlipidaemia, oedema, and variousglomerular changes, occurring mainly in children in 15–20% of whom the condition is steroid-resistant. About 85%of patients with steroid-resistant nephrotic syndrome(SRNS) exhibit renal histology of focal segmental glomer-ulosclerosis (FSGS), and the rest exhibit mesangial prolif-erative glomerulonephritis (MsPGN) or other rarerhistological phenotypes [1]. Mutations in the NPHS2 gene,encoding podocin, which is one of the important proteins ofthe slit diaphragm, are a frequent cause of sporadic SRNSin children, occurring in 2.8–28% of the cases [2–4].Mutations in exons 8 and 9 of the WT1 gene have also beenreported (more frequently in girls) with isolated SRNS [5].Other genes that are responsible have been recentlyreported, accounting for rare cases of SRNS.Idiopathic nephrotic syndrome is a frequent glomerulardisease in Cyprus and Greece, where 15–20% of cases aresteroid resistant, in accordance with the literature. In thiswork we studied for the first time in Greece and Cyprus acohort of 24 children (ten boys, 14 girls) with SRNS. Renalhistology, based on 1–3 biopsies, showed changes in FSGSin 21 children and MsPGN in three children. We investi-gated these children at the molecular level by searching formutations in the NPHS2 and WT1 (exons 8 and 9) genes. Indoing so, we used, for the first time to our knowledge,SURVEYOR endonuclease (Transgenomic, UK), an en-zyme that cleaves double-stranded DNA at positions ofheteroduplex mismatches, as a method for identifyingmutations and/or polymorphic variants. For this, genomicsequences, amplified by polymerase chain reaction (PCR)and encompassing the exons, the consensus exon