Abstract
BACKGROUND: Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5. Although mutation screening in the genes responsible for AS is typically performed, only a small proportion of patients receive genetic testing in China, and the functional consequences of multiple splicing variants in AS patients have not been investigated. METHODS: A family with X-linked AS was diagnosed based on family history and pathological findings from a kidney biopsy. Targeted next-generation sequencing was used to identify the causative mutation, and a minigene assay was performed to test the influence of the mutation on splicing. RESULTS: A c.834+2T>G in COL4A5 was identified and shown to co-segregate with AS in the family. The variant is located in the canonical splicing site and is predicted to induce aberrant splicing. Minigene assay using HEK 293T cells indicated the skipping of exon 14 in -COL4A5. CONCLUSIONS: The novel COL4A5 splicing mutation identified in the current study broadened the genetic spectrum of X-linked AS and further deepened our insight of the disease's molecular mechanism.