Dowling-Degos disease (DDD), or reticular pigmented anomaly of the flexures, is a type of rare autosomal-dominant genodermatosis characterized by reticular hyperpigmentation and hypopigmentation of the flexures, such as the neck, axilla, and areas below the breasts and groin, and shows considerable heterogeneity. Loss-of-function mutations of keratin 5 (KRT5) have been identified in DDD individuals. In this study, we collected DNA samples from a large Chinese family affected by generalized DDD and found no mutation of KRT5. We performed a genome-wide linkage analysis of this family and mapped generalized DDD to a region between rs1293713 and rs244123 on chromosome 20 [corrected]. By exome sequencing, we identified nonsense mutation c.430G>T (p.Glu144(∗)) in POFUT1, which encodes protein O-fucosyltransferase 1, in the family. Study of an additional generalized DDD individual revealed the heterozygous deletion mutation c.482delA (p.Lys161Serfs(∗)42) in POFUT1. Knockdown of POFUT1 reduces the expression of NOTCH1, NOTCH2, HES1, and KRT5 in HaCaT cells. Using zebrafish, we showed that pofut1 is expressed in the skin and other organs. Morpholino knockdown of pofut1 in zebrafish produced a phenotype characteristic of hypopigmentation at 48 hr postfertilization (hpf) and abnormal melanin distribution at 72 hpf, replicating the clinical phenotype observed in our DDD individuals. At 48 and 72 hpf, tyrosinase activities decreased by 33% and 45%, respectively, and melanin protein contents decreased by 20% and 25%, respectively. Our findings demonstrate that POFUT1 mutations cause generalized DDD. These results strongly suggest that the protein product of POFUT1 plays a significant and conserved role in melanin synthesis and transport.

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Objective: Mask plays an important role in preventing infectious respiratory diseases. The influence of wearing masks in physical exercise on the human body needs to be studied. The purpose of this study is to explore the influence of wearing surgical masks on the cardiopulmonary function of healthy people during exercise.Methods: The physiological responses of 71 healthy subjects (35 men and 36 women, age 27.77 ± 7.76 years) to exercises with and without surgical masks (mask-on and mask-off) were analyzed. Cardiopulmonary function and metabolic reaction were measured by the cardiopulmonary exercise test (CPET). All tests were carried out in random sequence and should be completed in 1 week.Results: The CPETs with the mask-on condition were performed undesirably (p < 0.05), and the Borg scale was higher than the mask-off (p < 0.001). Rest oxygen uptake (V.O2) and carbon dioxide production (V.CO2) with the mask-on condition were lower than mask-off (p < 0.01), which were more obvious at peak exercise (V.O2peak: 1454.8 ± 418.9 vs. 1628.6 ± 447.2 ml/min, p < 0.001; V.CO2peak: 1873.0 ± 578.7 vs. 2169.9 ± 627.8 ml/min, p = 0.005), and the anaerobic threshold (AT) brought forward (p < 0.001). At different stages of CPET with the mask-on condition, inspiratory and expiratory time (Te) was longer (p < 0.05), and respiratory frequency (Rf) and minute ventilation (V.E) were shorter than mask-off, especially at peak exercise (Rfpeak: 33.8 ± 7.98 vs. 37.91 ± 6.72 b/min, p < 0.001; V.Epeak: 55.07 ± 17.28 vs. 66.46 ± 17.93 l/min, p < 0.001). VT was significantly lower than mask-off just at peak exercise (1.66 ± 0.45 vs. 1.79 ± 0.5 l, p < 0.001). End-tidal oxygen partial pressure (PetO2), end-tidal carbon dioxide partial pressure (PetCO2), oxygen ventilation equivalent (V.E/V.O2), and carbon dioxide ventilation equivalent (V.E/V.CO2) with mask-on, which reflected pulmonary ventilation efficiency, were significantly different from mask-off at different stages of CPET (p < 0.05), but no significant difference in percutaneous oxygen saturation (SpO2) was found. Differences in oxygen pulse (V.O2/HR), oxygen uptake efficiency slope (OUES), work efficiency (△V.O2/△W), peak heart rate (HR), and peak systolic blood pressure (BP) existed between two conditions (p < 0.05).Conclusion: Wearing surgical masks during aerobic exercise showed certain negative impacts on cardiopulmonary function, especially during high-intensity exercise in healthy young subjects. These results provide an important recommendation for wearing a mask at a pandemic during exercises of varying intensity. Future research should focus on the response of wearing masks in patients with related cardiopulmonary diseases.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease that is primarily characterized by multiple café au-lait spots (CALs) and skin neurofibromas, which are attributed to defects in the tumor suppressor NF1. Because of the age-dependent presentation of NF1, it is often difficult to make an early clinical diagnosis. Moreover, identifying genetic alterations in NF1 patients represents a complex challenge. Currently, there are no effective detective methods, and no comprehensive NF1 mutation data are available for mainland China. We screened 109 Chinese patients from 100 families with NF1-like phenotypes (e.g., CALs, neurofibromas, etc.) using Sanger sequencing, multiplex ligation-dependent probe amplification and cDNA sequencing. NF1 mutations were identified in 97 individuals, among which 34 intragenic mutations have not previously been reported. Our exhaustive mutational analysis detected mutations in 89% (89/100) of the NF1-like probands and 93% (70/75) of subjects fulfilling the National Institutes of Health (NIH) criteria. Our findings indicate that individuals who exclusively present with multiple CALs exhibit a high possibility (76%) of having NF1 and show a significantly lower mutation rate (p = 0.042) compared with subjects who fulfill the NIH criteria, providing clinicians with the information that subjects only with multiple CALs harbor a considerable possibility (24%) of being attributed to other comparable diseases.

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