A homozygous cathepsin C mutation associated with Haim-Munk syndrome

Abstract

Haim-Munk syndrome (HMS) is a rare autosomal recessive disorder characterized clinically by abnormal palmoplantar hyperkeratosis and destruction of the periodontium, with hallmarks of onychogryphosis and arachnodactyly. Germline mutations in the lysosomal protease cathepsin C gene (CTSC) have been described in a single patient with HMS and in several individuals with the clinically related disorder Papillon-Lefevre syndrome (PLS). We describe a patient with HMS. We have analysed the cathepsin C gene in the proband and her mother. Sequence analysis of CTSC in the proband revealed a homozygous mutation at codon 196 (587T-->C) within exon 4 that altered the conserved leucine to proline (Leu196Pro), whereas the patient's mother was heterozygous for that mutation. The same mutation has previously been described in an unrelated Brazilian family with PLS. An identical single missense mutation in the cathepsin C gene may underlie both PLS and HMS. These findings confirm that HMS and PLS are allelic variants of cathepsin C gene mutations and suggest that other factors (environmental or genetic) may be important determinants of the clinical phenotype of HMS and PLS.

Haim Munk syndrome and Papillon Lefevre syndrome – allelic mutations in cathepsin C with variation in phenotype

“…Our patient was diagnosed as HMS, as apart from periodontitis and palmoplantar keratoderma he had onychogryphosis, arachnodactyly and pes planus. HMS has also been reported from Brazil 6 and Pakistan 7 . Hart et al.…”

Functional Cathepsin C mutations cause different Papillon–Lefèvre syndrome phenotypes

“…For example, specific CTSC mutations such as the p.Y347C mutation have been identified in PLS as well as in PAP (Toomes et al 1999, Hart et al 2000c, Hewitt et al 2004). Additionally, identical mutations were described in PLS and in the closely related HMS (Hart et al 2000b, Allende et al 2001, Cury et al 2002, 2005). Thus, HMS may also represent a variable phenotypic spectrum of CTSC mutations (Taibjee et al 2005).…”

Cytokine production by leukocytes of Papillon–Lefèvre syndrome patients in whole blood cultures

“…For example, specific CTSC mutations such as the p.Y347C mutation have been identified in PLS as well as in isolated prepubertal periodontitis [13,26]. Additionally, identical mutations have been found in PLS and in the closely related Haim-Munk syndrome [46][47][48]. The p.G301S and the p.R272P mutation, which was discovered in typical PLS families [12-14, 17, 26, 44, 49, 50], have been also associated with atypical cases, late onset of periodontitis [45] and mild skin lesions [16].…”