1. ¹Département de Dermatologie, Hôpital Saint André, Bordeaux, France
2. ²INSERM E0217, Université Victor Segalen, Bordeaux, France
3. ³Laboratoire de Génétique Humaine, Université Victor Segalen Bordeaux 2, Bordeaux, France
4. ⁴Département de Biochimie, CHU Pellegrin, Bordeaux, France
5. ⁵INSERM U466, Département de Biochimie, Maladies Métaboliques, CHU Rangueil, Toulouse, France
6. ⁶Département de Génétique, Hôpital Bretonneau, Tours, France
7. ⁷Département de Dermatologie, Hôpital Claude Huriez, Lille, France
8. ⁸Service d'Endocrinologie et Maladies Métaboliques, CHU Lille, Lille, France

Correspondence: Dr Thomas Jouary, Département de Dermatologie, Hôpital Saint André, 1, Rue Jean Burguet, 33075 Bordeaux cedex, France. E-mail: thomas.jouary@chu-bordeaux.fr

⁹These authors contributed equally to the work

Received 2 February 2007; Revised 26 April 2007; Accepted 30 April 2007; Published online 18 October 2007.

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.