Biallelic Variants in Lanosterol Synthase (LSS) Cause Palmoplantar Keratoderma-Congenital Alopecia Syndrome Type 2.

Palmoplantar keratoderma-congenital alopecia syndrome type 2 is an autosomal recessive disorder with an unknown genetic basis. In this study, we identified biallelic variants in the LSS gene in two unrelated palmoplantar keratoderma-congenital alopecia syndrome type 2 cases (c.3G>A, p.Met1? and c.1025T>G, p.Ile342Ser in patient 1; c.1522G>T, p.Gly508Trp and c.428+42T>A in patient 2) presenting with additional clinical features, including early-onset cataracts, pseudoainhum, and agenesis of the corpus callosum. LSS encodes lanosterol synthase (LSS), which functions in the cholesterol biosynthesis pathway by converting (S)-2,3-oxidosqualene to lanosterol. The c.3G>A variant resulted in an alternative translation initiation at residue Met81, producing an N-terminal truncated protein (LSS-ΔN80), as shown by immunoblotting. The c.428+42T>A variant introduced a potential splicing site, leading to a premature stop codon. Ex vivo studies revealed downregulation of LSS in both patients. Remarkably decreased lanosterol levels were found in vitro in three LSS variants, LSS-ΔN80, p.Ile342Ser, and p.Gly508Trp, suggesting a loss of enzymatic activity. Transmission electron microscopy and immunofluorescence showed abnormal cornified envelope formation in the stratum corneum of the patients. Taken together, our findings indicate LSS as a causative gene for palmoplantar keratoderma-congenital alopecia syndrome type 2, which emphasizes the importance of the cholesterol synthesis pathway in human skin cornification.

The application of 595-nm pulsed dye laser for vascular anomalies in a Chinese population: a 10-year experience.

BACKGROUND: The 595-nm pulsed dye laser (PDL) has been used to treat vascular anomalies for about 30 years; however, there are insufficient data in Chinese patients concerning therapeutic efficacy, optimized parameters, and procedure techniques. OBJECTIVE: To study the efficacy and relevant factors in PDL therapy for vascular anomalies in Chinese patients. METHOD: We enrolled 431 patients with 8 different vascular anomalies and no previous treatment in this retrospective study. A detailed classification of vascular anomalies and various parameters and techniques of PDL were studied. The clinical outcomes were analysed using the Investigator Global Assessment. RESULTS: Improvements were significantly correlated with infantile haemangioma (IH) subtypes (p < 0.05). A significant correlation between efficacy and lesion colour, anatomical sites, and hypertrophic-type port-wine stain (PWS) was found (p < 0.05). There was no significant correlation between efficacy and age or sex (p > 0.05). CONCLUSION: PDL is an effective and safe therapeutic modality for managing vascular anomalies in Chinese patients. We determined that differentiating and identifying IH subtypes prior to treatment could be a useful parameter for predicting therapeutic results.  Lesion colour, sites, and hypertrophic changes in PWS are relevant therapeutic factors. PDL parameters and techniques differ according to the various vascular anomalies to achieve optimal results.