Journal of Biotechnology & Biomaterials
Open Access

Abstract

Familial Glomerular Microscopic Hematurias (GMH) comprises a genetically heterogeneous group of conditions which include the Alport Syndrome (AS) and Thin Basement Membrane Nephropathy (TBMN), with mutations in the COL4A3/A4/A5 genes. We investigated patients from 57 undiagnosed Greek-Cypriot families consecutively referred to our center. We included families with at least three affected members that presented with GMH, with or without additional symptoms such as proteinuria or Chronic Renal Failure (CRF). We aimed to study the prevalence of COL4A3/A4 mutations and correlate the genotype to the phenotype. We had biopsies from patients belonging to 22/57 families (38.6%). 16/57 (28.1%) families featured heterozygous COL4A3/A4 mutations. Eleven families showed founder mutations, previously encountered in Cyprus, namely COL4A3-p. (G1334E) (8 families), COL4A3-p. (G871C) (2 families) and COL4A4-c.3854delG (1 family). The remaining five showed new mutations: COL4A3-p. (G484R), COL4A3-p. (G1077D), COL4A3-c.2621-2622delGAinsT, COL4A4-p. (G143V) and COL4A4-p. (G208D). Among all 16 families there were 87 mutation carriers (38M, 43%), while biopsies were available from patients in 8 families and showed TBMN and focal segmental glomerulo sclerosis. Altogether, 10 subjects among 87 heterozygous patients (11.5%) reached End-Stage Kidney Disease (ESKD) (at ages 37-69-yo, mean 50.1-yo). Forty-three patients (49.4%) had only MH and the rest had additional proteinuria and/or CRF/ESKD. These findings raise the total number of study Cypriot families with GMH to 68 with 27 showing heterozygous COL4A3/A4 mutations (39.7%). The clinical outcome of these patients substantiates that heterozygous COL4A3/A4 mutations predispose highly to FSGS and CRF/ESKD. In fact, TBMN may emerge as a more frequent cause of FSGS and ESKD than any other monogenic disorder.

Biography

Email: deltas@ucy.ac.cy