Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients
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BRIEF REPORT
Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients Kandai Nozu & Rafal Przybyslaw Krol & Yasufumi Ohtsuka & Koichi Nakanishi & Norishige Yoshikawa & Yoshimi Nozu & Hiroshi Kaito & Kyoko Kanda & Yuya Hashimura & Yuhei Hamasaki & Kazumoto Iijima & Masafumi Matsuo
Received: 29 February 2008 / Revised: 4 April 2008 / Accepted: 21 April 2008 / Published online: 27 June 2008 # IPNA 2008
Abstract Alport syndrome is the most common form of hereditary nephritis, and the majority of cases are caused by mutations in the COL4A5 gene. However, direct sequencing by polymerase chain reaction (PCR), from genomic DNA, or reverse transcriptase-polymerase chain reaction (RT-PCR), from mRNA, or polymerase chain reaction– single-strand conformation polymorphism (PCR-SSCP) has reportedly resulted in detection rates of 31% to 84%, but of only 20% to 71% when restricted to female patients. This report concerns two female patients with X-linked Alport syndrome. Although mutational analysis of the COL4A5 gene was conducted with direct sequencing using genomic DNA and mRNA extracted from leukocytes, the results
were negative for detection of mutations. Semi-quantitative PCR using genomic DNA was therefore conducted to detect large heterozygous deletions. The results were that the first patient showed complete loss of the COL4A5 gene and the second patient showed deletion from exons 37 to 51. Our patients possessed large heterozygous deletions in the COL4A5 gene that could not be detected with the standard direct sequencing method and were identified with semiquantitative PCR. Previously reported mutation detection rates for female patients have been lower than overall rates. Our findings indicate that this difference may, in part, be due to failure to detect this type of mutation with conventional analytical methods. Keywords Alport syndrome . COL4A5 . Large heterozygous deletion . Semi-quantitative PCR . Female
Kandai Nozu, Rafal Przybyslaw Krol and Yasufumi Ohtsuka contributed equally to this study. K. Nozu (*) : R. Przybyslaw Krol : Y. Nozu : H. Kaito : K. Kanda : Y. Hashimura : M. Matsuo Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunokicho 7-5-1, Chuo, Kobe 650-0017 Hyogo, Japan e-mail: [email protected] Y. Ohtsuka : Y. Hamasaki Department of Pediatrics, Saga Medical School, Saga, Japan K. Nakanishi : N. Yoshikawa Department of Pediatrics, Wakayama Medical University, Wakayama, Japan K. Iijima Department of Nephrology, National Center for Child Health and Development, Tokyo, Japan
Introduction Alport syndrome (AS) is a hereditary disorder that generally runs a progressive course. It usually presents in children as hematuria and proteinuria, associated with neurosensory deafness, and progresses to end-stage renal failure (ESRF) [1]. AS is genetically heterogeneous and appears in the Xlinked form of the syndrome with both autosomal dominant and autosomal recessive modes of inheritance [1]. However, approximately 85% of AS cases show X-linked inherit
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