Hereditary spastic paraplegia (HSP) is a heterogeneous inherited disorder that manifests with lower extremity weakness and spasticity. HSP can be inherited by autosomal dominant, autosomal recessive, and X-linked inheritance patterns. Recent studies have shown that, although rare, mutations in a single gene can lead to multiple patterns of inheritance of HSP. We enrolled the HSP family showing autosomal dominant inheritance and performed genetic study to find the cause of phenotype in this family. We recruited five members of a Korean family as study participants. Four of the five family members had pure HSP. Part of the family members underwent whole-exome sequencing (WES) to identify the causative mutation. As the result of WES and Sanger sequencing analysis, a novel missense mutation (c.452 C > T, p.Ala151Val) of ERLIN2 gene was identified as the cause of the autosomal dominant HSP in the family. Our study suggests that the ERLIN2 gene leads to both autosomal recessive and autosomal dominant patterns of inheritance in HSP. Moreover, autosomal dominant HSP caused by ERLIN2 appears to cause pure HSp in contrast to autosomal recessive ERLIN2 related complicated HSP (SPG18). Hereditary spastic paraplegia (HSP) is a heterogeneous disease that manifests clinically as lower extremity weakness and spasticity. It is divided into two types, complicated and pure, and the complicated type shows additional neurological symptoms, such as ataxia, seizure, cognitive decline, extrapyramidal symptoms, and peripheral neuropathy 1. Currently, more than 80 causal genes or loci have been identified and 75-80% of these are autosomal dominant, 25-30% are autosomal recessive, and 1-2% are X-linked 2. A few studies have shown that mutations in Endoplasmic Reticulum Lipid Raft-Associated 2 (ERLIN2) gene cause autosomal recessive HSP and one recent study suggested that ERLIN2 causes autosomal dominant HSP in two unrelated Caucasian families 2,3. Here, we describe an Asian family with pure autosomal dominant HSP caused by a novel ERLIN2 mutation that segregated among the family members. Results Clinical presentation. The proband was a 53-year-old male who presented with progressive gait disturbance. The patient noticed running difficulties as a teenager, began to use a single cane in his 30's, and was wheelchair-bound in his 50's. He had an autosomal dominant family history (Fig. 1A), and his mother, younger sister, and brother also experienced gait disturbance and difficulty walking. The initial neurological examination of the proband showed grade 3-4 lower limb weakness according to the Medical Research Council Scale with
Atopic dermatitis (AD) is a common chronic inflammatory skin disease, affecting 10-20% of individuals worldwide. Therefore, the discovery of drugs for treating AD is an attractive subject and important to human health. Diospyros kaki and Diospyros kaki (D. kaki) folium exert beneficial effects on allergic inflammation. However, the effect of D. kaki calyx on AD remains elusive. The present study evaluated the effects of an aqueous extract of D. kaki calyx (AEDKC) on AD-like skin lesions using mouse and keratinocyte models. We used a mouse AD model by the repeated skin exposure of house dust mite extract [Dermatophagoides farinae extract (DFE)] and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, to determine the underlying mechanism of its operation, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated keratinocytes (HaCaT) were used. Oral administration of AEDKC decreased AD-like skin lesions, as demonstrated by the reduced ear thickness, serum immunoglobulin E (IgE), DFE-specific IgE, IgG2a, histamine level and inflammatory cell infiltration. AEDKC inhibited the expression of pro-inflammatory cytokines and a chemokine via downregulation of nuclear factor-κB and signal transducer and activator of transcription 1 in HaCaT cells. On examination of the AD-related factors in vivo and in vitro, it was confirmed that AEDKC decreased AD-like skin lesions. Taken together, the results suggest that AEDKC is a potential drug candidate for the treatment of AD.
Several human studies have reported that capsaicin has anti-pruritic effects. Moreover, several concentrations of topical capsaicin have been used to alleviate itch. The aim of this study was to investigate the anti-pruritic effect of capsaicin against histamine-induced pruritus compared with that of topical steroid or vehicle in 15 healthy beagles. Fifteen dogs were divided into three groups (n = 5 each), and treated topically with one of the following on the left side of the neck: capsaicin, positive control (steroid), or negative control (vehicle). Each treatment was performed twice daily for 8 days. All dogs were injected with histamine intradermally before treatment and on the 2nd, 4th, 6th, and 8th days of the treatment to evoke itch. Pruritus, wheal, and erythema intensity were assessed at each evaluation; cutaneous temperature was also recorded. On the final day, skin biopsy was conducted for histopathological evaluation for all dogs. The severity of pruritus was lesser in the capsaicin-treated group compared with the negative control group on day 8 (p<0.05). In the capsaicin and steroid groups, wheal size, erythema index, and cutaneous temperature also decreased compared with pretreatment. Histopathological evaluation showed that the capsaicin-treated group had a higher number of inflammatory cells in the dermis compared to the vehicle control group; however, the steroid-treated group showed less severe inflammatory reactions than the vehicle control group. These results suggest that capsaicin cannot reduce inflammation but may play a helpful role in reducing pruritus in dogs.
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