ESPN 51th Annual Meeting

ESPN 2018


 
Frequency of Pathogenic Variants in a Munich Cohort of Patients with Alport Syndrome
EVA PAULINE MACHEROUX 1 ROBIN SATANOVSKIJ 2 KORBINIAN MARIA RIEDHAMMER 1 ROMAN G√úNTHNER 2 MATTHIAS BRAUNISCH 2 OLIVER GROSS 3 LUTZ RENDERS 2 JULIA HOEFELE 1

1- INSTITUTE OF HUMAN GENETICS, KLINIKUM RECHTS DER ISAR, TECHNICAL UNIVERSITY OF MUNICH, MUNICH, GERMANY
2- DEPARTMENT OF NEPHROLOGY, KLINIKUM RECHTS DER ISAR, TECHNICAL UNIVERSITY OF MUNICH, MUNICH, GERMANY
3- CLINIC OF NEPHROLOGY AND RHEUMATOLOGY, UNIVERSITY MEDICAL CENTER GOETTINGEN, UNIVERSITY OF GOETTINGEN, GOETTINGEN, GERMANY
 
Introduction:

Alport syndrome (AS) is an inherited kidney disorder leading to end-stage renal disease. Extrarenal symptoms may include hearing loss and ocular changes. AS is caused by pathogenic variants in the genes COL4A3COL4A4, and COL4A5Approximately 85% of the patients show an X-linked inheritance due to variants in COL4A5AS can also be inherited in an autosomal recessive (about 15% of the cases) or autosomal dominant (very rare) pattern if variants in COL4A3 or COL4A4 genes are present. Next-generation sequencing (NGS) has become a useful tool for detection of pathogenic variants in heterogeneous disorders. The aim of this study was to evaluate the frequency of pathogenic variants in a Munich cohort of patients with Alport syndrome.

Material and methods:

The clinical phenotype of the patients was collected using a standardized questionnaire. Mutational analysis was performed by exome sequencing (ES).

Results:

The study population consisted of 56 unrelated families with a total of 153 individuals, 40/153 were healthy, 113/153 suffered from Alport syndrome or Alport syndrome related symptoms. Mutational analysis was performed in 42 of the families by ES so far. In 32/42 families variants in known genes associated with Alport syndrome have been identified (76%). Biallelic variants were detected in 7/32 families (22%) in COL4A3 and 2/32 (6%) in COL4A4, hetero-/hemi-/homozygous variants in 23/32 (72%) in COL4A5. 2/32 families (6%) presented with the histological phenotype of focal segmental glomerulosclerosis (FSGS). Their causative variants were located in COL4A3 and COL4A5, respectively. Furthermore, in one family a new candidate gene has been identified.

Conclusions:

The detection rate observed in our patient cohort is comparable to the frequency described in the literature. Interestingly, one family with a variant in COL4A5 presented with FSGS. ES is a powerful technique of diagnostics in patients with an Alport phenotype and is able to identify candidate genes in hereditary kidney diseases.