title: Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients.
abstract: BACKGROUND
  Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans.
  
  
  METHODS
  To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population.
  
  
  RESULTS
  Patients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33.
  
  
  CONCLUSIONS
  The novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.
authors: Faculty of Biological and Chemical Sciences, Doctoral Program in Biotechnology and Master Program in Biomedical Sciences, Autonomous University of Sinaloa, Culiacán, México.
authors: José G
authors: JG
authors: Romero-Quintana
authors: Luis O
authors: LO
authors: Frías-Castro
authors: Eliakym
authors: E
authors: Arámbula-Meraz
authors: Maribel
authors: M
authors: Aguilar-Medina
authors: Jesús E
authors: JE
authors: Dueñas-Arias
authors: Jesús D
authors: JD
authors: Melchor-Soto
authors: José G
authors: JG
authors: Romero-Navarro
authors: Rosalío
authors: R
authors: Ramos-Payán
mesh_terms: D000293:Adolescent; D000328:Adult; D020789:Cathepsin C / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009154:Mutation; D010214:Papillon-Lefevre Disease / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; C533918:CTSC protein, human; D020789:Cathepsin C