title: Molecular testing for adult type Alport syndrome.
abstract: BACKGROUND
  Alport syndrome (AS) is a progressive renal disease with cochlear and ocular involvement. The majority of AS cases are X-linked (XLAS) and due to mutations in the COL4A5 gene. Although the disease may appear early in life and progress to end stage renal disease (ESRD) in young adults, in other families ESRD occurs in middle age. Few of the more than four hundred mutations described in COL4A5 are associated with adult type XLAS, but the families may be very large.
  
  
  METHODS
  We classified adult type AS mutation by prevalence in the US and we developed a molecular assay using a set of hybridization probes that identify the three most common adult type XLAS mutations; C1564S, L1649R, and R1677Q.
  
  
  RESULTS
  The test was validated on samples previously determined to contain one or none of these mutations. In the US, the test's clinical specificity and sensitivity are estimated to be higher than 99% and 75% respectively. Analytical specificity and sensitivity are above 99%.
  
  
  CONCLUSIONS
  This test may be useful for presymptomatic and carrier testing in families with one of the mutations and in the diagnosis of unexplained hematuria or chronic kidney disease.
authors.affiliation: ARUP institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA. pontkig@aruplab.com
authors.forename: Genevieve
authors.initials: G
authors.lastname: Pont-Kingdon
authors.forename: Kelli
authors.initials: K
authors.lastname: Sumner
authors.forename: Friederike
authors.initials: F
authors.lastname: Gedge
authors.forename: Chris
authors.initials: C
authors.lastname: Miller
authors.forename: Joyce
authors.initials: J
authors.lastname: Denison
authors.forename: Martin
authors.initials: M
authors.lastname: Gregory
authors.forename: Elaine
authors.initials: E
authors.lastname: Lyon
mesh_terms: D000328:Adult; D000367:Age Factors; D019943:Amino Acid Substitution / Q000235:genetics; D024141:Collagen Type IV / Q000235:genetics*; D024062:Collagen Type V / Q000235:genetics*; D015342:DNA Probes / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV; D024062:Collagen Type V; D015342:DNA Probes