COL4A5 and LAMA5 variants co-inherited in familial hematuria: digenic inheritance or genetic modifier effect?

Background: About 40-50% of patients with familial microscopic hematuria (FMH) caused by thin basement membrane nephropathy (TBMN) inherit heterozygous mutations in collagen IV genes (COL4A3, COL4A4). On long follow-up, the full phenotypic spectrum of these patients varies a lot, ranging from isolated MH or MH plus low-grade proteinuria to chronic renal failure of variable degree, including end-stage renal disease (ESRD).

Methods: Here, we performed Whole Exome Sequencing (WES) in patients of six families, presenting with autosomal dominant FMH, with or without progression to proteinuria and loss of renal function, all previously found negative for severe collagen IV mutations.

Iron deposits in the knee joints of a thalassemic patient.

The overall prognosis for patients with β-thalassemia has improved considerably during the past decades mainly due to regular blood transfusions, improvements in chelation therapy, and enhanced surveillance with imaging studies examining iron overload and other clinical complications. However, the prolonged survival of these patients leads to the development of other health problems including degenerative diseases such as arthropathies, which require further attention since they have a significant impact on the quality of life. In the current case report, we present a 45-year-old white man with β-thalassemia complaining of non-traumatic pain and restriction in the range of motion of both knees.