Editor—Alport syndrome is characterised by a progressive glomerulonephritis with typical ultrastructural changes in the glomerular basement membrane. The most frequent, semidominant, X linked type is the result of a variety of mutations (either point mutations or intragenic deletions) of the COL4A5 gene encoding the α5 chain of type IV collagen.1

During SSCP scanning of the COL4A5 gene, a shift in a segment including exon 44 and flanking intronic sequences was found in a 19 year old proband showing typical ultrastructural changes of the glomerular basement membrane (III.3 in fig 1). Sequence analysis showed a G→C transversion in the 5′ splice site of intron 44 (position 4271+1). The mutation introduced an AluI restriction site which divided a 66 bp fragment into two fragments of 39 + 27 bp. All 18 family members were tested using this restriction assay and the mutation was found in the proband's affected brother, his cousin, his mother, and two maternal aunts. Surprisingly, the proband's grandmother was a normal homozygote. The proband's grandfather was dead, but true paternity of all daughters could be (indirectly) ascertained by polymorphic markers.4

In this family the mutation is associated with juvenile Alport syndrome in males, suggesting …