A Novel Mutation in a Japanese Family with X-linked Alport Syndrome

Abstract

We herein report a novel mutation in a Japanese family with an X-linked Alport syndrome (AS) mutation in COL4A5. Patient 1 was a 2-year-old Japanese girl. She and her mother (patient 2) had a history of proteinuria and hematuria without renal dysfunction, deafness, or ocular abnormalities. Pathological findings were consistent with AS, and a genetic analysis revealed that both patients had a heterozygous mutation (c.2767G>C) in exon 32. In summary, the identification of mutations and characteristic pathological findings was useful in making a diagnosis of AS. For a close long-term follow-up, the early detection and treatment of women with X-linked AS are important.

Last Nucleotide Substitutions of COL4A5 Exons Cause Aberrant Splicing

“…Among 578 missense variants, 14 (2.4%) pathogenic variants caused by single-base substitutions at the last nucleotide positions in exons were included in this study (Figure 1 and Table 1). 5, [24][25][26][27][28][29][30][31][32][33][34][35][36] In addition, 6 novel variants in our cohort were included. Finally, 20 variants were included in this study.…”

A Systematic Review of Pathogenic COL4A5 Variants and Proteinuria in Women and Girls With X-linked Alport Syndrome

“…15 However, studies of X-inactivation in humans are difficult to interpret, in part because X-inactivation patterns vary in affected tissues and the peripheral blood cells that are usually assayed. [16][17][18][19] The lack of genotype-phenotype correlation in women and girls with X-linked Alport syndrome manifests also as the large intrafamilial variability of the age at kidney failure, compared with male relatives. 9 Any genotype-phenotype correlation is considered less pronounced in females than in males, and that therefore larger cohorts are required to demonstrate a relationship.…”

“… 15 Nevertheless, studies in humans are difficult to interpret, in part because X-inactivation patterns vary in different affected tissues and the peripheral blood cells that are usually examined. 16 , 17 , 18 , 19 …”

A family case of X-linked Alport syndrome patients with a novel variant in COL4A5

“…Differences in X-chromosome inactivation may affect disease severity. Abe et al identified a novel variation in a Japanese family using X-chromosome inactivation assays [ 10 ]. Yamamura et al demonstrated that the phenotype of female XLAS patients is not always mild, and the mechanisms determining the severity of female XLAS are multifactorial [ 11 ].…”