[Identification of pathogenic mutations in two Chinese families affected with primary localized cutaneous amyloidosis].

OBJECTIVE To identify potential mutations in two Chinese families affected with primary localized cutaneous amyloidosis. METHODS Peripheral blood samples of the family were collected with informed consent. Genomic DNA was extracted with a phenol chloroform method. All of the 17 exons and their flanking splicing sites of the OSMR gene were amplified with PCR and subjected to Sanger sequencing. Suspected mutations were verified with PCR - restriction fragment length polymorphism and high-resolution melting assays. RESULTS A missense mutation (c.1538G>A) was found in exon 10 of the OSMR gene in all of the six patients from family 1. A missense mutation (c.2081C>T) was found in exon 14 of the OSMR gene in all of the four patients from family 2. The same mutations were not found among the healthy controls. CONCLUSION Two missense mutations (c.1538G>A and c.2081C>T) were detected in the OSMR gene in two Chinese families affected with primary localized cutaneous amyloidosis. Our findings have further confirmed the pathogenicity of such mutations.

Actinic Prurigo in Singaporean Chinese: A Positive Association with HLA-DRB1*03:01.

Studies have reported the association of human leukocyte antigen (HLA) genes with susceptibility to develop actinic prurigo (AP) in Caucasians, but there were no studies in Asian populations, including the Chinese. Our study was performed to determine if AP is associated with susceptibility or protective HLA alleles or haplotypes in Singaporean Chinese. All Chinese patients diagnosed with AP at National Skin Center, Singapore, from January 2002 to April 2015 were invited to participate in the study. Clinical data and phototesting results were collated, and HLA typing was performed. Among 14 patients included, 11 were male and the mean age was 49.6 (37.9-61.3) years. All patients did not have a family history of AP and none had mucosal involvement, as such these clinical features differed from Caucasian AP patients. The frequency of DRB1*03:01 in AP patients was significantly higher compared to healthy controls (43% vs 16%, P = 0.022, odds ratio (OR) 3.89). Concurrently, the frequency of HLA-B*58:01-DRB1*03:01 haplotype was also significantly increased (25% vs 7%, P = 0.004, OR 4.23). In conclusion, HLA-DRB1*03:01 was associated with AP in Singaporean Chinese patients. This novel allelic association may possibly be utilized as a biological marker to aid in the diagnosis of AP in Chinese patients.

The elusive gene for keratolytic winter erythema.

Keratolytic winter erythema (KWE), also known as Oudtshoorn skin disease, is characterised by a cyclical disruption of normal epidermal keratinisation affecting primarily the palmoplantar skin with peeling of the palms and soles, which is worse in the winter. It is a rare monogenic, autosomal dominant condition of unknown cause. However, due to a founder effect, it occurs at a prevalence of 1/7 200 among South African Afrikaans-speakers. In the mid-1980s, samples were collected from affected families for a linkage study to pinpoint the location of the KWE gene. A genome-wide linkage analysis, using microsatellite markers, identified the KWE critical region on chromosome 8p23.1-p22. Subsequent genetic studies focused on screening candidate genes in this critical region; however, no pathogenic mutations that segregated exclusively with KWE were identified. The cathepsin B (CTSB) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) genes revealed no potentially pathogenic variants, nor did they show differential gene expression in affected skin. Mutation detection in additional candidate genes also failed to identify the KWE-associated variant, suggesting that the causal variant may be in an uncharacterised functional region. Bioinformatic analysis revealed highly conserved regions within the KWE critical region and a custom tiling array was designed to cover this region and to search for copy number variation. Although the study did not identify a variant that segregates exclusively with KWE, it provided valuable insight into the complex KWE-linked region. Next-generation sequencing approaches are being used to comb the region, but the causal variant for this interesting hyperkeratotic palmoplantar phenotype still remains elusive. 

Clinical characteristics of adult-onset actinic prurigo in Asians: a case series.

BACKGROUND: Actinic prurigo (AP) is a chronic, pruritic skin condition caused by an abnormal reaction to sunlight. AIMS: The aim of this study is to determine the clinical characteristics of AP in patients attending the National Skin Centre, Singapore, from 1 st January 1999 to 30 th June 2008. METHODS: Cases of AP diagnosed from 1 st January 1999 to 30 th June 2008 were retrieved from the center's electronic medical records and analyzed. RESULTS: A total of 11 patients were diagnosed with AP. The mean age at diagnosis was 52 years. There were 9 (82%) Chinese and 2 (18%) Malay patients. Nine (82%) were male and 2 (18%) were female. The most commonly affected areas were the face, forearms, and hands (72%). Phototesting showed reduced minimal erythema dose (MED) to ultraviolet A (UVA) in 5 (46%) patients, both UVA and ultraviolet B (UVB) in 4 (36%) patients and UVB in 1 (9%) patient. Seven (64%) patients reported partial improvement after treatment with a combination of topical corticosteroids and sunscreens. Four (36%) patients received systemic therapy with partial response. CONCLUSION: Adult-onset AP is more common in the Asian population, with a male predominance. The face, forearms, and hands are the most commonly affected areas. The absence of mucosal involvement is also a distinguishing feature between the Asian and Caucasian population. Close to half of the patients have reduced MED to UVA on phototesting. The prognosis for AP is poor as it tends to run a chronic course with suboptimal response to treatment.