title: A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations.
abstract: BACKGROUND
  Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or uniparental disomy. We describe here a 20-year-old woman who inherited two different COL4A5 variants, one from her father (c.2677G>C) and one from her mother (c.384 +1 G>A).
  
  
  METHODS
  The index case had normal renal function, proteinuria and no clinically detectable hearing loss, or ocular abnormalities. Her father and paternal uncle developed end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central retinopathy. Her mother had mildly impaired renal function, proteinuria, hearing loss, but no ocular abnormalities. Her maternal grandfather and 22-year-old brother, both with this mutation, developed renal failure by 28 years with hearing loss, or had proteinuria and hearing loss respectively.
  
  
  CONCLUSIONS
  The index case has clinical features consistent with germ cell mosaicism of two COL45A mutations associated with adult-onset renal failure, but no ocular abnormalities. Her risk of renal failure is high, but the rate of progression to end-stage disease depends on the underlying mutations, and disease modification with renin-angiotensin blockade.
authors: Melbourne Health, The University of Melbourne, Parkville, VIC, 3050, Australia.
authors: Mardhiah
authors: M
authors: Mohammad
authors: Ranjit
authors: R
authors: Nanra
authors: Deb
authors: D
authors: Colville
authors: Paul
authors: P
authors: Trevillian
authors: Yanyan
authors: Y
authors: Wang
authors: Helen
authors: H
authors: Storey
authors: Frances
authors: F
authors: Flinter
authors: Judy
authors: J
authors: Savige
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D024141:Collagen Type IV / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D050172:Genes, X-Linked; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D009030:Mosaicism; D009154:Mutation; D009394:Nephritis, Hereditary / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D051437:Renal Insufficiency / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV