Molecular testing for adult type Alport syndrome.
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.
Pont-Kingdon
Genevieve
G
ARUP institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA. pontkig@aruplab.com
Sumner
Kelli
K
Gedge
Friederike
F
Miller
Chris
C
Denison
Joyce
J
Gregory
Martin
M
Lyon
Elaine
E
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
C478159:COL4A5 protein, human; D024141:Collagen Type IV; D024062:Collagen Type V; D015342:DNA Probes