Neurofibromatosis type 1 (NF1) is a tumor-predisposition disorder that arises due to pathogenic variants in tumor suppressor NF1. NF1 has variable expressivity that may be due, at least in part, from heritable elements such as modifier genes; however, few genetic modifiers have been identified to date.
In this study, we performed a genome-wide association analysis of the number of café-au-lait macules (CALM) that are considered a tumor-like trait as a clinical phenotype modifying NF1.
A borderline genome-wide significant association was identified in the discovery cohort (CALM1, N = 112) between CALM number and rs12190451 (and rs3799603, r2  = 1.0; p = 7.4 × 10-8 ) in the intronic region of RPS6KA2. Although, this association was not replicated in the second cohort (CALM2, N = 59) and a meta-analysis did not show significantly associated variants in this region, a significant corroboration score (0.72) was obtained for the RPS6KA2 signal in the discovery cohort (CALM1) using Complementary Pairs Stability Selection for Genome-Wide Association Studies (ComPaSS-GWAS) analysis, suggesting that the lack of replication may be due to heterogeneity of the cohorts rather than type I error.
rs12190451 is located in a melanocyte-specific enhancer and may influence RPS6KA2 expression in melanocytes-warranting further functional studies.

UNASSIGNED: The application of fractional Q-switched ruby laser (FQSRL) or intense pulsed light (IPL) on Café-au-lait macule (CALM) is rational and the data are lacking.
UNASSIGNED: To evaluate the efficacy and safety of FQSRL and IPL in CALM.
UNASSIGNED: The patients with CALM who were treated with FQSRL or IPL were retrospectively observed from April 2016 to April 2019. The laser/light treatments were conducted at an interval of 3-4 weeks.
UNASSIGNED: For FQSRL (N = 67), 88.23%, 95.46%, 100% patients achieved >50% improvement by three sessions, four sessions, and more than four sessions of treatment, respectively. A better and better efficacy was shown with the increasing number of sessions (χ2 = 89.51, p < .01). For IPL (N = 54), 45% and 87.5% achieved >50% improvement by three sessions and more than four sessions of treatments, respectively. More than four sessions achieved better efficacy than less sessions (p < .01). Under various time-points, FQSRL presented more favorable responses than IPL (p < .05). All the adverse effects were tolerable and acceptable.
UNASSIGNED: FQSRL or IPL would be an alternative and safe modality for CAML in Chinese patients.