TY - JOUR
T1 - The role of molecular genetics in diagnosing familial hematuria(s)
AU - Deltas, Constantinos
AU - Pierides, Alkis
AU - Voskarides, Konstantinos
N1 - Funding Information:
The authors thank the patients and relatives who participated in the numerous studies that made this research possible. This work was supported by the Medical and Public Health Services of the Cyprus Ministry of Health and by grants from the Cyprus Research Promotion Foundation ΠΕΝΕΚ ΕΝΙΣΧ/0505/02, ΠΕΝΕΚ/ΕΝΙΣΧ/0308/08, NEW INFRASTRUCTURE/STRATEGIC/0308/24, and through the University of Cyprus Articles 3/311 and 3/346 to CD.
PY - 2012/8
Y1 - 2012/8
N2 - Familial microscopic hematuria (MH) of glomer-ular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). A mutation in CFHR5, a member of the complement factor H family of genes that regulate complement activation, was recently shown to cause isolated C3 glomerulopathy, presenting with MH in childhood and demonstrating a significant risk for CKD/ ESKD after 40 years old. Through these results molecular genetics emerges as a powerful tool for a definite diagnosis when all the above conditions enter the differential diagnosis, while in many at-risk related family members, a molecular diagnosis may obviate the need for another renal biopsy.
AB - Familial microscopic hematuria (MH) of glomer-ular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). A mutation in CFHR5, a member of the complement factor H family of genes that regulate complement activation, was recently shown to cause isolated C3 glomerulopathy, presenting with MH in childhood and demonstrating a significant risk for CKD/ ESKD after 40 years old. Through these results molecular genetics emerges as a powerful tool for a definite diagnosis when all the above conditions enter the differential diagnosis, while in many at-risk related family members, a molecular diagnosis may obviate the need for another renal biopsy.
KW - Alport syndrome
KW - C3 glomerulonephritis
KW - CFHR5 nephropathy
KW - Collagen IV
KW - Complement
KW - Familial hematuria
KW - Microscopic hematuria
KW - Thin Basement Membrane Nephropathy
UR - http://www.scopus.com/inward/record.url?scp=84863984599&partnerID=8YFLogxK
U2 - 10.1007/s00467-011-1935-5
DO - 10.1007/s00467-011-1935-5
M3 - Review article
C2 - 21688191
AN - SCOPUS:84863984599
SN - 0931-041X
VL - 27
SP - 1221
EP - 1231
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 8
ER -