TY - JOUR
T1 - COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy
AU - Voskarides, Konstantinos
AU - Damianou, Loukas
AU - Neocleous, Vassos
AU - Zouvani, Ioanna
AU - Christodoulidou, Stalo
AU - Hadjiconstantinou, Valsamakis
AU - Ioannou, Kyriacos
AU - Athanasiou, Yiannis
AU - Patsias, Charalampos
AU - Alexopoulos, Efstathios
AU - Pierides, Alkis
AU - Kyriacou, Kyriacos
AU - Deltas, Constantinos
PY - 2007/11
Y1 - 2007/11
N2 - Mutations in the COL4A3/COL4A4 genes of type IV collagen have been found in ∼40% of cases of thin basement membrane nephropathy, which is characterized by microscopic hematuria and is classically thought to cause proteinuria and chronic renal failure rarely. Here we report our observations of 116 subjects from 13 Cypriot families clinically affected with thin basement membrane nephropathy. These families first came to our attention because they segregated microscopic hematuria, mild proteinuria, and variable degrees of renal impairment, but a dual diagnosis of focal segmental glomerulosclerosis (FSGS) and thin basement membrane nephropathy was made in 20 biopsied cases. Molecular studies identified founder mutations in both COL4A3 and COL4A4 genes in 10 families. None of 82 heterozygous patients had any extrarenal manifestations, supporting the diagnosis of thin basement membrane nephropathy. During follow-up of up to three decades, 31 of these 82 patients (37.8%) developed chronic renal failure and 16 (19.5%) reached end-stage renal disease. Mutations G1334E and G871C were detected in seven and three families, respectively, and were probably introduced by founders. We conclude that these particular COL4A3/COL4A4 mutations either predispose some patients to FSGS and chronic renal failure, or that thin basement membrane nephropathy sometimes coexists with another genetic modifier that is responsible for FSGS and progressive renal failure. The findings presented here do not justify the labelling of thin basement membrane nephropathy as a benign condition with excellent prognosis.
AB - Mutations in the COL4A3/COL4A4 genes of type IV collagen have been found in ∼40% of cases of thin basement membrane nephropathy, which is characterized by microscopic hematuria and is classically thought to cause proteinuria and chronic renal failure rarely. Here we report our observations of 116 subjects from 13 Cypriot families clinically affected with thin basement membrane nephropathy. These families first came to our attention because they segregated microscopic hematuria, mild proteinuria, and variable degrees of renal impairment, but a dual diagnosis of focal segmental glomerulosclerosis (FSGS) and thin basement membrane nephropathy was made in 20 biopsied cases. Molecular studies identified founder mutations in both COL4A3 and COL4A4 genes in 10 families. None of 82 heterozygous patients had any extrarenal manifestations, supporting the diagnosis of thin basement membrane nephropathy. During follow-up of up to three decades, 31 of these 82 patients (37.8%) developed chronic renal failure and 16 (19.5%) reached end-stage renal disease. Mutations G1334E and G871C were detected in seven and three families, respectively, and were probably introduced by founders. We conclude that these particular COL4A3/COL4A4 mutations either predispose some patients to FSGS and chronic renal failure, or that thin basement membrane nephropathy sometimes coexists with another genetic modifier that is responsible for FSGS and progressive renal failure. The findings presented here do not justify the labelling of thin basement membrane nephropathy as a benign condition with excellent prognosis.
UR - http://www.scopus.com/inward/record.url?scp=35848944448&partnerID=8YFLogxK
U2 - 10.1681/ASN.2007040444
DO - 10.1681/ASN.2007040444
M3 - Article
C2 - 17942953
AN - SCOPUS:35848944448
SN - 1046-6673
VL - 18
SP - 3004
EP - 3016
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 11
ER -