br Papillon Lef vre syndrome PLS

Papillon–Lefèvre syndrome (PLS), also named keratosis palmoplantar with periodontopathia (OMIM 245000), was first described by Papillon and Lefèvre in 1924. The condition occurs with a frequency of 1–4:1,000,000. It is an autosomal recessive disorder which is characterized by a diffuse palmoplantar hyperkeratosis and rapidly progressive and devastating periodontitis that results in the premature loss of both the poly ic teeth and the permanent teeth. Other clinical manifestations consist of calcification of dura mater, recurrent infections, liver abscess, nail abnormalities, bone mature obstruction, thyroid enlargement, microphthalmia, hyperglycemia, hypertension, and mental retardation. Toomes et aland Hart et al found () gene mutations in PLS families. In addition, they discovered a virtual loss of activity in PLS patients and significantly reduced activity in obligate carriers. is a lysosomal protease whose activation is important to the body\'s defenses. We identified a novel nonsense mutation in the gene in a Chinese PLS family. The study was approved by the ethics committee of the Shandong University and according to Declaration of Helsinki Principles. A 15-year-old Chinese girl presented with severe periodontitis and palmoplantar hyperkeratosis at birth. She got infections repeatedly and had several scars on the eyelids and the upper chest (A). Her younger brother has the same disorder. Her parents\' phenotype was normal and they were not consanguineous (A). Physical examination revealed that erythema extended the whole body. She had lost her teeth and all teeth were artificial teeth except for one (B). Her palms and soles were scaly, and there were plaques with scales on her elbows (D, 1F, and 1G). All of her nails were yellow with thickening (C and 1E). Ultrasound image showed the girl was suffering from uronephrosis of the right kidney (H). She had no urinary system symptoms before, and did not know herself that she was suffering from uronephrosis. After obtaining written informed consent, DNA was isolated from peripheral blood leucocytes and gene mutational analysis was performed as described. The proband in this kindred was found to be homozygous for a C>A transition at nucleotide 774 (c. 774 C>A; B), resulting in p. C258X. Her brother (affected) had the same mutation and her parents were carriers with heterozygous mutation at nucleotide 774 (c. 774 C>A; C,D,E). These sequence variants were not detected in 100 healthy controls (F). In this study, we identified a novel nonsense mutation in the gene in the PLS family. The mutation is located at the enzyme active site in exon 6 of the gene. It affects the disulfide bonds of the CTSC polypeptide. It is predicted as producing a truncated protein (only 258 amino acids) that does not have normal enzyme activity (G). Our data further expands the spectrum of mutations in the gene underlying PLS. The proband presented with repeated skin infections and right uronephrosis besides the characteristic clinical features. A previous report presented that pyogenic liver abscess is increasingly recognized as a complication of PLS because of impairment of the immune system. Morgan et al reported a 5-year-old girl with PLS who presented with a renal abscess. Therefore, we consider patients exhibiting increased susceptibility to various infections such as periodontitis, skin abscesses, and systemic infections. The repeated skin infections may result from the weakened immune system. In addition, it is the first report that shows that PLS patients are complicated by uronephrosis. The relationship between the mutation and uronephrosis is not clear. A further functional study of is emerging. Acknowledgments This work was funded by the Shandong Province science and technology development plan (2011GSF11847 and 2010GSF10812), and the Natural Science Foundation of China (81171492/H1102).