Nephropathy With Pretibial Epidermolysis Bullosa And Deafness

A number sign (#) is used with this entry because of evidence that this syndrome is caused by mutation in the CD151 gene (602243).

Clinical Features

Kagan et al. (1988) described 2 sibs with an apparently unique association of hereditary nephritis, epidermolysis bullosa, and beta-thalassemia minor. The sibs were a 19-year-old boy and his 17-year-old sister (of an 'oriental Jewish' family). They had been on hemodialysis for 5 years and continuous ambulatory peritoneal dialysis for 1 year, respectively. Both showed multiple recurrent infected skin blisters of the legs followed by atrophy, nail dystrophy, bilateral lacrimal duct stenosis, sensorineural deafness, proteinuria in the nephrotic range, and anemia due to beta-thalassemia minor.

Molecular Genetics

Karamatic Crew et al. (2004) demonstrated that the sibs described by Kagan et al. (1988) and a third patient were negative for the MER2 blood group antigen (see 179620), which is expressed by the CD151 gene (602243). All 3 were homozygous for a 1-bp insertion in the CD151 gene, causing frameshift and a premature stop signal, with the resultant truncated protein lacking the integrin-binding domain (602243.0001). Pretibial epidermolysis bullosa (131850) can be caused by mutation in the COL7A1 gene (120120), but renal disease and deafness are unassociated. Association of deafness and nephropathy suggested Alport syndrome, which is usually inherited as an X-linked disorder (301050) and caused by mutation in the COL4A5 gene (303630). Autosomal recessive Alport syndrome (203780) is caused by mutation in the COL4A3 (120070) or COL4A4 (120131) genes.