Detection of an intragenic deletion expands the spectrum of CTSC mutations in Papillon-Lefèvre syndrome.

[papillon-lefèvre syndrome]

The Papillon-Lefèvre syndrome (PLS ) is an autosomal recessive disorder . The gene responsible for the disease , cathepsin C (CTSC ), is localized in 11 q 14 .1 -q 14 .21 . We performed mutational and functional analyses of CTSC in two patients affected by this condition . Three previously unreported CTSC mutations were identified . The first patient had a compound heterozygous status with a p .G 386 R missense mutation and an intragenic deletion spanning exons 3 -7 . Second patient carried a homozygous splice site mutation , p .A 253 SfsX 30 . CTSC activity was undetectable in both patients , thus demonstrating the pathological effect of these mutations . We describe early evidence of an original intragenic deletion reported in PLS . Since this mutational mechanism could not be detected by direct sequencing , intragenic deletion has to be specifically investigated using gene dosage analysis techniques such as quantitative multiplex fluorescent polymerase chain reaction . We consider that this technique should be performed in patients with apparently homozygous CTSC mutations when one parent does not carry the expected mutation or is not available for analysis .