title: 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.
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: V F
authors.initials: VF
authors.lastname: Cury
authors.forename: R S
authors.initials: RS
authors.lastname: Gomez
authors.forename: J E
authors.initials: JE
authors.lastname: Costa
authors.forename: E
authors.initials: E
authors.lastname: Friedman
authors.forename: W
authors.initials: W
authors.lastname: Boson
authors.forename: L
authors.initials: L
authors.lastname: De Marco
mesh_terms: D000328:Adult; D020789:Cathepsin C / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010214:Papillon-Lefevre Disease / Q000235:genetics; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: D020789:Cathepsin C