Rapid detection and prevalence of the AGT deletion/insertion mutation underlying autosomal recessive renal tubular dysgenesis.

Abstract

Background: A homozygous deletion/insertion (del/ins) mutation (NM_000029.3: c.1365_c.1777delinsTTGCCTTGC) in the AGT gene responsible for autosomal recessive renal tubular dysgenesis (ARRTD) is frequently reported in Taiwan. Rapid and accurate detection of this peculiar mutation is crucial for genetic counseling and knowledge of the allele frequency in the population may help to better characterize the a priori risk for ARRTD.

Methods: Using a TaqMan probe-based real-time polymerase chain reaction, we designed a mutation detection plate for the c.1365_c.1777delinsTTGCCTTGC mutation of the AGT gene, with Sanger sequencing as the reference standard. The allelic frequency of heterozygous AGT mutation was determined in 5000 healthy subjects. Demographic data and serum AGT, angiotensin I (AgI), and AgII concentrations were collected in 2 affected patients, 20 carriers, and 9 normal subjects.

Results: The designed detection plate, thoroughly validated by direct sequencing, showed perfect sensitivity and specificity in genetically-diagnosed patients, carriers, and healthy subjects. The overall allelic frequency of positive AGT heterozygosity was 1 % (50/5000). There was a significantly higher serum AGT concentration in heterozygous AGT carriers than wild-type subjects despite no difference in blood pressure.

Conclusion: This del/ins mutation in AGT can be rapidly and accurately identified by this allele-specific mutation plate. Due to its high prevalence in the Taiwanese population, it is likely that ARRTD may be more common in Taiwan than previously thought.