A family with X-linked Alport syndrome confirmed by skin biopsy.

Sir, Type-IV collagen is a major structural component of basement membranes. Six type-IV collagen chains, a1(IV) to a6(IV), have been identified w1x. The a1(IV) and a2(IV) chains are present in all basement membranes. The a3(IV), a4(IV), a5(IV), and a6(IV) chains are expressed selectively in the basement membranes of some tissues, such as kidney, cochlea, and eye. Alport syndrome (AS) is a hereditary nephritis caused by defects in type-IV collagen in glomerular basement membranes (GBM), and it is characterized by a progressive glomerulonephritis associated with extrarenal features including auditory and ocular abnormalities w1,2x. AS is classified as X-linked (XL) form, autosomal recessive (AR) form, and autosomal dominant (AD) form. The XL form is associated with mutations in the COL4A5 gene w2x. The AR form is caused by COL4A3 or COL4A4 gene mutations w2x. Genetic mutation detection has become the ultimate and sufficient diagnostic criterion of AS. However, gene analysis in patients with AS remains a tedious and sometimes unsuccessful task because the incriminated genes contain more than 50 exons and there are no hot spots. In the meantime , the study of skin biopsy provides valuable diagnostic information in some patients with XL-AS, because the epidermal basement membrane (EBM) normally contains a5(IV) w1–3x. This method is easier than gene analysis. Here we report a family with XL-AS, which was confirmed by skin biopsy. We also discuss about extrarenal abnormalities and histological differential diagnosis in our patients. Cases. Case 1, a 19-year-old Japanese man, was admitted to our hospital for initiation of the administration of continuous ambulatory peritoneal dialysis (CAPD). He was the only child of case 2. His maternal grandmother was diagnosed as having chronic glomerulonephritis, but a renal biopsy was not performed. At the age of 2, he underwent a renal biopsy because of persistent haematuria and proteinuria. Light microscopy showed diffuse mild mesangial proliferative glomerulonephritis. Immunofluorescent studies demonstrated no staining for immunoglobulins or complement. Electron microscopy disclosed diffuse thin GBM. At this time, he was diagnosed as having non-IgA glomerulo-nephritis with thin GBM. His renal function gradually decreased, and reached end-stage renal disease (ESRD) 14 years later. Keratoconus was observed, but a hearing defect was not detected by an audiogram. Case 2 was a 43-year-old Japanese woman. At the age of 29, she received a renal biopsy because of persistent haematuria and proteinuria with mild renal impairment. Light microscopy showed diffuse mild to moderate mesangial proliferation and segmental sclerosis. …