RESUMO
Papillon-Lefèvre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low-cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss-of-function mutation in CTSC, indicating that they suffer from a PLS-like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.
Assuntos
Catepsina C/urina , Doença de Papillon-Lefevre/diagnóstico , Doença de Papillon-Lefevre/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Catepsina C/genética , Catepsina C/metabolismo , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto JovemRESUMO
Oral-facial-digital syndrome VI (OFD6 OMIM #277170), also called Varadi-Papp syndrome, is a ciliopathy inherited in an autosomal recessive pattern. Recently, mutations in C5orf42 (OMIM #614571) have been associated with OFD6. OFD6 overlaps with Joubert syndrome and mutations in C5orf42 were described in Joubert syndrome 17 (JBTS17, OMIM #614571). Using exome sequencing we report three novel variants and one previously reported variant in the C5orf42 gene in patients with OFD6.
