ESPN 51th Annual Meeting

ESPN 2018


 
NOVEL MUTATIONS AND VARIATIONS IN TURKISH CHILDREN WITH ALPORT SYNDROME: ARE THE BENIGN VARIATIONS ALWAYS HARMLESS?
NESLIHAN CICEK 1 NURDAN YILDIZ 1 PINAR ATA 2 IBRAHIM GOKCE 1 MEHTAP SAK 1 HANDAN KAYA 3 HARIKA ALPAY 1

1- MARMARA UNIVERSITY MEDICAL SCHOOL, DEPARTMENT OF PEDIATRIC NEPHROLOGY, ISTANBUL, TURKEY
2- MARMARA UNIVERSITY MEDICAL SCHOOL, DEPARTMENT OF GENETICS, ISTANBUL, TURKEY
3- MARMARA UNIVERSITY MEDICAL SCHOOL, DEPARTMENT OF PATHOLOGY, ISTANBUL, TURKEY
 
Introduction:

 

AlportSyndrome(AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes encoding α3,α4,α5 chains of type IV collagen. There may still be undetected mutations and variations that can cause Alport syndrome. 

We aimed to evaluate the effect of mutations and variations on the clinical phenotype and to report novel mutations that may be effective in the clinical course of AS patients.

Material and methods:

 

We retrospectively analyzed the clinical characteristics, pathologic findings, treatments and genetic analysis of the patients with AS, and evaluated the genotype-phenotype correlation.

Results:

 

Thirty-eight patients(23females, 15males) were included into the study. The mean age at admission and the mean follow-up time were 9.14±4.31(2.9-17.4) and 3.85±2.59(0.1-10.2) years, respectively.Twenty-two pathogenic mutations and 24 variations were found, and 8 of these patients have both a pathogenic mutation and a variation. The variation in COL4A4(c.3979G>A; p.Val1327 Met) was the most common variation found in  20 patients. No pathogenic mutation was found in 13 of 20 patients and eight of them were presented with proteinuria, three with hematuria and two with parenchymal hyperechogenity on ultrasonography. Two novel mutations [one hemizygous in COL4A5(c.2870delC; p.Pro957Glnsf*39) and one in COL4A3(c.1015G>C; p.Gly339Arg)] were detected in two patients who have microscopic hematuria with massive proteinuria and macroscopic hematuria with nephritic range proteinuria, respectively. A previously unreported heterozygous variation in COL4A3(c.3211-30G>A) was detected in one patient with nephritic range proteinuria.

Conclusions:

 

According to our results, two novel mutations we found in COL4A3(c.1015G>C; p.Gly339Arg) and COL4A5(c.2870delC; p.Pro957Glnsf*39) may effect the renal phenotype of AS. In addition, COL4A4(c.3979G>A; p.Val1327 Met) variation that was previously reported benign may have pathogenicity. However, we need further large deletion/duplication studies of the COL4A3/A4/A5 genes.