Supplementary Material for: Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport
syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are
kidney diseases that differ in clinical diagnosis, treatment, and
prognosis. Nevertheless, they may result from the same causative genes.
Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg,
p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different
collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS,
and FSGS. Using bioinformatics analyses and pedigree verification, we
show that these novel variants are pathogenetic and cosegregate with
TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type
IV-associated kidney disease phenotypes are heterogeneous, with
overlapping pathology and genetic mutations. We propose that COL4A4-associated
TBMN, ADAS, and FSGS should be considered as collagen type IV kidney
disease subtypes that represent different phases of disease progression.