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Mosaicism in Alport syndrome and genetic counselling
  1. MIRELLA BRUTTINI*,
  2. FRANCESCA VITELLI*,
  3. ILARIA MELONI*,
  4. GIUSEPPE RIZZARI,
  5. MARIO DELLA VOLPE,
  6. GIANNA MAZZUCCO§,
  7. MARIO DE MARCHI,
  8. ALESSANDRA RENIERI*
  1. *Genetica Medica, Policlinico Le Scotte, Universita' di Siena, 53100 Siena, Italy
  2. †Ambulatorio Nisseno di Emodialisi, Caltanissetta, Italy
  3. ‡Nefrologia, Az Osp S S Antonio e Biagio e C Arrigo, Alessandria, Italy
  4. §Dipartimento di Scienze Biomediche e Oncologia Umana, Universita' di Torino, Italy
  5. ¶Dip Scienze Cliniche e Biologiche, Ospedale San Luigi Universita' di Torino, Italy
  1. Dr Renieri, renieri{at}unisi.it

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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

Figure 1

Pedigree of the family and haplotype analysis at the COL4A5/COL4A6 locus. *Presence of mutation G→C at 4271+1 of intron 44. For haplotype analysis: A=2B6 polymorphism at the 3′ end of the COL4A5 gene2; Y=A6YU2 polymorphism in intron 31 of COL4A6.3

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

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