Journal Article

Natural history of genetically proven autosomal recessive Alport syndrome

Yan, Kunimasa, Kaito, Hiroshi, Yoshikawa, Norishige, Fu, Xue Jun, Nozu, Kandai, Nakanishi, Koichi, Vorechovsky, Igor, Oka, Masafumi, Hashimura, Yuya, Morisada, Naoya, Matsuo, Masafumi, Iijima, Kazumoto

2014

Overview

Background Autosomal recessive Alport syndrome (ARAS) is a rare hereditary disease caused by homozygous or compound heterozygous mutations in either the COL4A3 or COL4A4 genes. Failure to diagnose ARAS cases is common, even if detailed clinical and pathological examinations are carried out. As the mutation detection rate for ARAS is unsatisfactory, we sought to develop more reliable diagnostic methods and provide a better description of the clinicopathological characteristics of this disorder. Methods A retrospective analysis of 30 genetically diagnosed patients with ARAS in 24 pedigrees was conducted. The mutation detection strategy comprised three steps: (1) genomic DNA analysis using polymerase chain reaction (PCR) and direct sequencing; (2) mRNA analysis using reverse transcription (RT)-PCR to detect RNA processing abnormalities; (3) semi-quantitative PCR using capillary electrophoresis to detect large heterozygous deletions. Results Using the three-step analysis, we identified homozygous or compound heterozygous mutations in all patients. Interestingly, 20 % of our ARAS patients showed normal expression of α5 in kidney tissue. The median age of developing end-stage renal disease was 21 years. Conclusions The strategy described in this study improves the diagnosis for ARAS families. Although immunohistochemical analysis of α5 can provide diagnostic information, normal distribution does not exclude the diagnosis of ARAS.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Adolescent / Adult / Alport's syndrome / Child / Child, Preschool / Chronic kidney failure / Collagen / Complications and side effects / Development and progression / DNA Mutational Analysis / Female / Gene mutations / Genetic Association Studies / Hematuria / Humans / Kidney diseases / Kidney Failure, Chronic - genetics / Male / Medical screening / Medicine / Medicine & Public Health / Microscopy / Mutation / Nephritis, Hereditary - diagnosis / Nephritis, Hereditary - genetics / Nephrology / Original Article / Pathology / Patients / Pediatrics / Polymerase Chain Reaction / Retrospective Studies / Risk factors / Urology / Young Adult