Naslov
Genotype-phenotype correlation for novel COL4A4 splice site mutation causing autosomal Alport spectrum disorders

Autori
Šenjug Petar ; Nikuševa Martić Tamara ; Šenjug Perica Marija ; Oroz Maja ; Horaček Matija ; Ćuk Martin ; Abdović Slaven ; Vlašić – Matas Jadranka ; Galešić Krešimir ; Galešić Ljubanović Danica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
31st European Congress of Pathology

Mjesto i datum
Nica, Francuska, 07.09.2019. - 11.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Alport syndrome ; COL4A4 splice site variant

Sažetak
Background & Objectives: Alport spectrum disorders are genetically heterogenic disorders caused by COL4A3, COL4A4 or COL4A5 mutations. Aim of this study was to correlate mutational status with pathohistological and clinical characteristics of patients with novel COL4A4 splice site mutation. Methods: Four patients, three male and one female, from four unrelated families (age range 2-61 years) with pathohistological diagnosis of Alport syndrome (AS) or thin glomerular basement membrane nephropathy (TBMN) were tested by NGS sequencing (Illumina MiSeq platform) for COL4A3, COL4A4 and COL4A5 genes mutations. Testing was performed as a part of project ''Genotype-Phenotype correlation in Alport’s syndrome and Thin Glomerular Basement Membrane Nephropathy'' founded by the Croatian Science Foundation. Novel splice acceptor pathogenic variant c.193-2A>C was found in COL4A4. The youngest patient was homozygous and others were heterozygous for the mutation. Results: All the patients presented with proteinuria and haematuria at the time of kidney biopsy. The homozygous patient in light microscopy had only increased number of immature glomeruli, while electron microscopy showed typical findings for AS. From the group of heterozygous patients, two showed focal segmental glomeruloscerosis in light microscopy. Electron microscopy revealed TBMN with focal lamellation in one patient, typical AS in second and TBMN in third patient. Conclusion: Diagnostic process of AS spectrum disorders can be challenging. Although genetic testing gives insight into potential disease severity and provides basis for genetic counselling there is variability in phenotype of disorders with the same mutation. Renal biopsy remains method that provides information about degree of renal parenchyma damage.

Izvorni jezik
Engleski

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