Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV [alpha]5 chain

• Published in: Kidney international Vol. 85; no. 5; p. 1208
• Main Authors: Hashimura, Yuya, Nozu, Kandai, Kaito, Hiroshi, Nakanishi, Koichi, Fu, Xue Jun, Ohtsubo, Hiromi, Hashimoto, Fusako, Oka, Masafumi, Ninchoji, Takeshi, Ishimori, Shingo, Morisada, Naoya, Matsunoshita, Natsuki, Kamiyoshi, Naohiro, Yoshikawa, Norishige, Iijima, Kazumoto
• Format: Journal Article
• Language: English
• Published: London Elsevier Limited 01.05.2014
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2013.479

X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain (α5(IV)). Complete absence of α5(IV) in the renal basal membrane is considered a pathological characteristic in male patients; however, positive α5(IV) staining has been found in over 20% of patients. We retrospectively studied 52 genetically diagnosed male X-linked Alport syndrome patients to evaluate differences in clinical characteristics and renal outcomes between 15 α5(IV)-positive and 37 α5(IV)-negative patients. Thirteen patients in the α5(IV)-positive group had non-truncating mutations consisting of nine missense mutations, three in-frame deletions, and one splice-site mutation resulting in small in-frame deletions of transcripts. The remaining two showed somatic mutations with mosaicism. Missense mutations in the α5(IV)-positive group were more likely to be located before exon 25 compared with missense mutations in the α5(IV)-negative group. Furthermore, urinary protein levels were significantly lower and the age at onset of end-stage renal disease was significantly higher in the positive group than in the negative group. These results help to clarify the milder clinical manifestations and molecular characteristics of male X-linked Alport syndrome patients expressing the α5(IV) chain.