Gentamicin ointment has potential in the treatment of Nagashima-type palmoplantar keratosis. However, there is a lack of reliable study data. The aim of this study was to perform a prospective, randomized, double-blinded, contralateral, vehicle-controlled clinical trial. A total of 20 subjects diagnosed with Nagashima-type palmoplantar keratosis by genetic test, who carried nonsense mutations, enrolled in the 30-day study. Gentamicin ointment was applied to the hand and foot on one side of the body, and vehicle ointment was applied to the hand and foot on the other side. The choice of hand and foot in each subject was randomly allocated. The severity of the patient’s skin lesions and quality of life were assessed by a blinded evaluator, using the Dermatology Life Quality Index, visual analogue scale scores and digital photography. Gentamicin ointment treatment resulted in a significant improvement in symptoms of hyperkeratosis and foul smell compared with vehicle. No difference was found in the effect on erythema between gentamicin and vehicle. In conclusion, gentamicin ointment demonstrated positive responses and good tolerance in treating Nagashima-type palmoplantar keratosis caused by nonsense mutations.

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis‐like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane‐bound transcription factor peptidase/site‐1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid β‐oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.

Focal facial dermal dysplasias type III (FFDD III), commonly known as Setleis syndrome (SS; Online Mendelian Inheritance in Man #227260), is a type of focal facial dermal dysplasia, characterized by bitemporal atrophic skin lesion. The homozygous mutations in the TWIST2 gene and copy number variants (CNV) at chromosome 1p36.22p36.21 were reported as the pathogenic mechanism. In this study, we collected DNA samples from a large Chinese family affected by FFDD and found no mutation of TWSIT2. To determine the underlying genetic cause, we performed a multipoint parameter linkage analysis and haplotype analysis of the family 1 and mapped SS to a region Chr1:14.074–20.524cM (rs2401090–rs2294642). Copy number variant was identified by Sanger sequencing, which breakpoints were Chr1:11695972 and Chr1:11829858. The region contains eight genes, including FBXO2, FBXO44, FBXO6, MAD2L2, DRAXIN, AK125437, AGTRAP, and C1orf167. There were no candidate gene mutations of the second family with SS. Our study further reduced the size of CNV resulting in SS (Chr1:11696993–11829858) and focused on eight genes.