Nitta Hiroshi, Wara-Aswapati Nawarat, Lertsirivorakul Jinda, Nakamura Tsutomu, Yamamoto Matsuo, Izumi Yuichi, Nakamura Toshiaki, Ishikawa Isao
Department of Comprehensive Oral Health Care, Behavioral Dentistry, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
J Periodontol. 2005 Mar;76(3):492-6. doi: 10.1902/jop.2005.76.3.492.
Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmar- plantar hyperkeratosis and rapid periodontal destruction of both primary and permanent dentitions. It has been shown that the disease is caused by cathepsin C gene (CTSC) mutation leading to the deficiency of cathepsin C enzymatic activity. This study demonstrates the clinical manifestations and CTSC mutational and enzymatic activity analyses in a 5-year-old Thai male PLS patient and his parents.
Peripheral blood samples were obtained for genomic DNA isolation. All exons of the CTSC gene were amplified by polymerase chain reaction (PCR) using specific primers. Mutations were identified by DNA sequencing. Verification of the mutation was performed by digestion of PCR products by restriction endonucleases. The cathepsin C enzymatic activity was determined using the synthetic substrate glycyl- L-arginine-7-amino-4-methylcoumarin.
The patient demonstrated classical characteristics of PLS, including hyperkeratotic skin lesions. By the age of 5, all of his primary teeth were extracted due to severe periodontal infection. The parents had no physical abnormalities. The periodontal examination revealed localized mild periodontal destruction. Sequence analysis showed a nucleotide change at position 90 from C >A (c.90C >A) which resulted in a change from cysteine residue to a premature stop codon at the amino acid position 30 in the exon 1. The HpyCH4V digestion revealed that the patient was homozygous, whereas both the father and mother were heterozygous carriers of this mutation. The cathepsin C activity was reduced in the patient's mother, and the activity in the patient was almost completely lost.
This is the first study to demonstrate a CTSC gene mutation in a Thai family with PLS. The identified mutation is novel and potentially leads to the drastic reduction of the cathepsin C enzymatic activity. This suggests that the mutation is pathogenetic, causing the PLS. Mutational analysis in more members of the family is warranted to identify whether the mutation is inherited from a common ancestor.
帕皮永-勒费弗尔综合征（PLS）是一种罕见的常染色体隐性疾病，其特征为掌跖角化过度以及乳牙和恒牙的快速牙周破坏。研究表明，该疾病由组织蛋白酶C基因（CTSC）突变导致组织蛋白酶C酶活性缺乏引起。本研究展示了一名5岁泰国男性PLS患者及其父母的临床表现、CTSC突变及酶活性分析。
采集外周血样本用于基因组DNA提取。使用特异性引物通过聚合酶链反应（PCR）扩增CTSC基因的所有外显子。通过DNA测序鉴定突变。通过限制性内切酶消化PCR产物对突变进行验证。使用合成底物甘氨酰-L-精氨酸-7-氨基-4-甲基香豆素测定组织蛋白酶C酶活性。
该患者表现出PLS的典型特征，包括角化过度性皮肤病变。5岁时，由于严重的牙周感染，他的所有乳牙均被拔除。其父母无身体异常。牙周检查显示局限性轻度牙周破坏。序列分析显示第90位核苷酸由C变为A（c.90C>A），导致外显子1中第30位氨基酸位置的半胱氨酸残基变为过早的终止密码子。HpyCH4V消化显示该患者为纯合子，而其父亲和母亲均为该突变的杂合携带者。患者母亲的组织蛋白酶C活性降低，而患者的活性几乎完全丧失。
这是首次在一个患有PLS的泰国家庭中证明CTSC基因突变的研究。所鉴定的突变是新的，可能导致组织蛋白酶C酶活性急剧降低。这表明该突变具有致病性，导致了PLS。有必要对该家族更多成员进行突变分析，以确定该突变是否从共同祖先遗传而来。
