Department of Dermatology and Venereology, Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia.
National Skin Center, Singapore, Singapore.
Int J Dermatol. 2017 Nov;56(11):1161-1168. doi: 10.1111/ijd.13776.
Mal de Meleda (OMIM# 248300; keratosis palmoplantaris transgrediens) is an autosomal recessive form of palmoplantar keratoderma, clinically characterized by sharp demarcated erythema and hyperkeratosis of the palms and soles that progress with age and extend to the dorsal aspects of the hands and feet. The mal de Meleda is caused by mutations in the SLURP1 gene that encodes secreted lymphocyte antigen 6/urokinase-type plasminogen receptor-related protein 1 (SLURP1). To date no reported cases from Indonesia. The aims of the study were to describe the typical features of mal de Meleda cases in a Javanese family in Indonesia and identify the mutation in the ARS B gene which encodes SLURP1.
In this study, three Javanese patients, siblings from nonconsanguineous nonaffected parents, presented with classical symptoms of mal de Meleda. Genetic analysis screening SLURP1 gene was conducted for the specimens from the patients and other family members.
A novel homozygous three-nucleotide deletion in exon 3, i.e. c.271-273TCTdel, was identified in the patients. Subcloning and sequencing revealed both parents (I.2 and I.3) and one of the father's siblings (I.1) carry heterozygous c.271-273TCTdel, while the other father's sibling (I.2), the mother's sister (I.4), and a healthy control matched the ethnicity of the family, showing normal sequence of the entire SLURP1.
This is the first mal de Meleda case of Javanese ethnicity to be documented, and the unique mutation has not previously been reported. The finding supports the notion that despite the rarity, SLURP1 mutation causing mal de Meleda is ubiquitous.
遗传性掌跖角化过度症（OMIM# 248300；掌跖角化过度移行症）是一种常染色体隐性遗传形式的掌跖角化病，临床上表现为手掌和脚底界限分明的红斑和过度角化，随着年龄的增长而逐渐加重，并扩展到手和脚的背部。遗传性掌跖角化过度症是由 SLURP1 基因的突变引起的，该基因编码分泌型淋巴细胞抗原 6/尿激酶型纤溶酶原激活物受体相关蛋白 1（SLURP1）。迄今为止，印度尼西亚尚无报道病例。本研究的目的是描述印度尼西亚爪哇家族中遗传性掌跖角化过度症病例的典型特征，并鉴定编码 SLURP1 的 ARS B 基因突变。
在这项研究中，3 名爪哇患者，来自非近亲非受累父母的兄弟姐妹，表现出遗传性掌跖角化过度症的典型症状。对患者和其他家庭成员的标本进行了 SLURP1 基因的遗传分析筛查。
在患者中发现了外显子 3 中 novel homozygous three-nucleotide deletion，即 c.271-273TCTdel。亚克隆和测序显示，父母双方（I.2 和 I.3）和父亲的一个兄弟姐妹（I.1）携带杂合 c.271-273TCTdel，而父亲的另一个兄弟姐妹（I.2）、母亲的妹妹（I.4）和一个与家族同种族的健康对照者，显示出整个 SLURP1 序列正常。
这是首例爪哇遗传性掌跖角化过度症病例，该突变尚未见报道。这一发现支持了尽管罕见，但 SLURP1 突变引起的遗传性掌跖角化过度症是普遍存在的观点。
