The risk of germline mosaicism in X-linked Alport syndrome: a case report

Abstract

Alport syndrome is a hereditary disease caused by abnormalities in type IV collagen. It is associated with progressive renal failure, hearing loss, and ocular abnormalities. Here, we report the case of a boy with X-linked Alport syndrome whose mother was suspected to have a germline mosaic mutation. A 2-year-old boy presented with persistent hematuria and proteinuria after gross hematuria. The results of renal biopsy showed, only minor changes under light microscopy, all fluorescence antibody tests were negative, and type IV collagen staining was negative for the α5 chain in both the glomerular basement membrane and Bowman’s capsule. Genetic analysis was requested, and a hemizygous mutation was identified in exon 49 of COL4A5, which was thought to be the etiology. Our patient was initially suspected of having de novo mutational X-linked Alport syndrome. However, the patient’s mother had persistent hematuria, and genetic analysis revealed a very small wave of single-nucleotide deletions, suggesting the possibility of germline mosaicism. In this case, more careful genetic counseling is recommended, including the possibility of passing it on to siblings. For a definitive diagnosis, it is important and practical to consider regular urinalysis screening of siblings and genetic analysis of the patient’s mother’s urinary cytoplasm.