Clinical and molecular analysis in Papillon-Lefevre syndrome

Author(s)

Machado, Renato A. ^[1] ; Cuadra-Zelaya, Florence J. M. ^{[1, 2]} ; Martelli-Junior, Hercilio ^[3] ; Miranda, Roseli T. ^[4] ; Casarin, V, Renato C. ; Correa, Monica G. ^[5] ; Nociti, Francisco ^[6] ; Coletta, Ricardo D. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Piracicaba, SP - Brazil

^[2] Univ El Salvador, Dept Oral Diag, San Salvador - El Salvador

^[3] Univ Montes Claros, Dent Sch, Stomatol Clin, Montes Claros, MG - Brazil

^[4] Univ Jose do Rosario Vellano, Sch Dent, Ctr Rehabil Craniofacial Anomalies, Alfenas, MG - Brazil

^[5] Univ Paulista, Sch Dent, Dent Res Div, Pinheiros, SP - Brazil

^[6] Casarin, Renato C., V, Univ Estadual Campinas, Sch Dent, Dept Prosthodont & Periodont, Div Periodont, Piracicaba, SP - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 179, n. 10 JULY 2019.
• Web of Science Citations: 0

Abstract

Papillon-Lefevre syndrome (PLS; MIM\#245000) is a rare recessive autosomal disorder characterized by palmar and plantar hyperkeratosis, and aggressively progressing periodontitis leading to premature loss of deciduous and permanent teeth. PLS is caused by loss-of-function mutations in the CTSC gene, which encodes cathepsin C. PLS clinical expressivity is highly variable and no consistent genotype-phenotype correlation has been demonstrated yet. Here we report the clinical and genetic features of five PLS patients presenting a severe periodontal breakdown in primary and permanent dentition, hyperkeratosis over palms and soles, and recurrent sinusitis and/or tonsillitis. Mutation analysis revealed two novel homozygous recessive mutations (c.947T>C and c.1010G>C) and one previous described homozygous recessive mutation (c.901G>A), with parents carrying them in heterozygous, in three families (four patients). The fourth family presented with the CTSC c.628C>T mutation in heterozygous, which was inherited maternally. Patient carrying the CTSC c.628C>T mutation featured classical PLS phenotype, but no PLS clinical characteristics were found in his carrier mother. All mutations were found to affect directly (c.901G>A, c.947T>C, and c.1010G>C) or indirectly (c.628C>T, which induces a premature termination) the heavy chain of the cathepsin C, the region responsible for activation of the lysosomal protease. Together, these findings indicate that both homozygous and heterozygous mutations in the cathepsin C heavy chain domain may lead to classical PLS phenotype, suggesting roles for epistasis or gene-environment interactions on determination of PLS phenotypes. (AU)

• FAPESP's process: 09/54068-0 - Acquisition of a capillary sequencer to meet the DNA sequencing needs of the professors and researchers at the State University of Campinas Faculty of Dentistry of Piracicaba
• Grantee: Ricardo Della Coletta
• Support Opportunities: Multi-user Equipment Program