Abstract
BackgroundAlport 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.MethodsWe 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.ResultsThe 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%.ConclusionThis 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.
Highlights
Alport syndrome (AS) is a progressive renal disease with cochlear and ocular involvement
Alport syndrome (AS) is a progressive inherited disease characterized by persistent hematuria that progresses to end stage renal disease (ESRD)
AS is due to defects in type IV collagen alpha chain 3, 4 or 5 encoded respectively by the COL4A3, COL4A4 and COL4A5 genes
Summary
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. Few of the more than four hundred mutations described in COL4A5 are associated with adult type XLAS, but the families may be very large. The majority (>80%) of AS is X-linked with mutations found in the COL4A5 gene [1]. More than 400 mutations causing XLAS have been described in COL4A5 http://www.arup.utah.edu/data base/ALPORT/ALPORT_welcome.php. Nonsense and frameshift mutations cause juvenile onset disease in most patients. Other mutations such as some splice variants and glycine substitutions in the GXY collagen repeats, in exons 1-20, confer later onset disease [2]. Amino acid substitutions in the N non-collagenous (NC1) domain of the (page number not for citation purposes)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
