title: Detection of an intragenic deletion expands the spectrum of CTSC mutations in Papillon-Lefèvre syndrome.
abstract: The Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder. The gene responsible for the disease, cathepsin C (CTSC), is localized in 11q14.1-q14.21. 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.G386R missense mutation and an intragenic deletion spanning exons 3-7. Second patient carried a homozygous splice site mutation, p.A253SfsX30. 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.
authors.affiliation: Département de Dermatologie, Hôpital Saint André, Bordeaux, France. thomas.jouary@chu-bordeaux.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouary
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupry
authors.forename: Isabelle
authors.initials: I
authors.lastname: Redonnet-Vernhet
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.forename: Ingrid
authors.initials: I
authors.lastname: Burgelin
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Delaporte
authors.forename: Claire
authors.initials: C
authors.lastname: Douillard
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.forename: Benoît
authors.initials: B
authors.lastname: Arveiler
mesh_terms: D000328:Adult; D020789:Cathepsin C / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D005820:Genetic Testing; D006801:Humans; D008297:Male; D010214:Papillon-Lefevre Disease / Q000175:diagnosis / Q000235:genetics*
chemical_list: D020789:Cathepsin C