3688 Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, NS, Canada.
7235 Division of Dermatology, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
J Cutan Med Surg. 2020 Jan/Feb;24(1):28-32. doi: 10.1177/1203475419878161. Epub 2019 Sep 16.
Punctate palmoplantar keratoderma type 1 (PPPK1) presents in late childhood to adulthood with multiple small discrete hyperkeratotic papules on palms and soles. PPPK1 is an autosomal dominant skin disease caused by mutations. It has been suggested that PPPK1 may be associated with an increased predisposition to systemic malignancies.
To evaluate the presence of mutations in Canadian families with PPPK1 and the possible increased predisposition to systemic malignancies.
Eighteen unrelated Canadian families with PPPK1 were recruited for this study. Genomic DNA was extracted from saliva and PCR amplification was performed for all exons and exon/intron junctions. PCR products were sequenced and analyzed for mutations. A family history of malignancy was obtained from the index case and, when possible, from other family members.
We have identified 5 heterozygous loss of function mutations in 11 families. The mutation c.370 C>T, p.Arg124* was the most prevalent and was identified in 6 families. A splice site mutation, c.451+3delAAGT, was identified in 2 families. The other mutations c.473delG, p.Gly158Glufs0; c.550-551insAAT, p.Gly183; and c.505-506 dupAA, p.Asn169Lysfs*6 were each identified in 1 family. Different cancers were reported in 11 families (Table 1 and Supplemental Figure S1).
mutations were found in 11 of 18 families with PPPK1. In some families there appears to be an association with cancer.
点状掌跖角化病 1 型（PPPK1）在儿童后期至成年期发病，表现为手掌和足底出现多个小而离散的角化过度丘疹。PPPK1 是一种常染色体显性遗传病，由 基因突变引起。有研究提示 PPPK1 可能与全身性恶性肿瘤的易感性增加有关。
评估加拿大 PPPK1 家系中 基因突变的存在情况，以及与全身性恶性肿瘤易感性增加的关系。
本研究共纳入 18 个无血缘关系的加拿大 PPPK1 家系。从唾液中提取基因组 DNA，对所有外显子及其内含子交界处进行 PCR 扩增。对 PCR 产物进行测序和突变分析。从先证者处获取恶性肿瘤家族史，如可能，还从其他家族成员处获取。
我们在 11 个家系中发现了 5 个杂合性 失功能突变。c.370 C>T，p.Arg124突变最为常见，在 6 个家系中被发现。另外 2 个家系存在剪接位点突变 c.451+3delAAGT。其他 3 个家系分别存在 c.473delG，p.Gly158Glufs0；c.550-551insAAT，p.Gly183*；c.505-506dupAA，p.Asn169Lysfs*6 突变。11 个家系报告了不同的癌症（表 1 和补充图 S1）。
在 18 个 PPPK1 家系中发现了 11 个家系存在 基因突变。在一些家系中，似乎与癌症有关。
