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Background: Café-au-lait macules (CALMs) in neurofibromatosis type 1 (NF1) are an early and accessible phenotype in NF1, but have not been extensively studied.Objective: We sought to more fully characterize the phenotype of CALMs in patients with NF1.Methods: In all, 24 patients with a diagnosis of NF1 confirmed through clinical diagnosis or molecular genetic testing were recruited from patients seen in the genetics department at the University of Alabama at Birmingham. CALM locations were mapped using standard digital photography. Pigment intensity was measured with a narrowband spectrophotometer, which estimates the relative amount of melanin based on its absorption of visible light. The major response was defined as the difference between the mean melanin from the CALM and the mean melanin from the surrounding skin. The major response for each spot was compared with spots within an individual and across individuals in the study population.Results: There was significant variability of the major response, primarily attributable to intrapersonal variability (48.4%, P < .0001) and secondly to interpersonal variability (33.0%, P < .0094). Subsequent analysis based on genetic mutation type showed significantly darker spots in individuals with germline mutations leading to haploinsufficiency.Limitations: The study was performed on a small population of patients and the method has not yet been used extensively for this purpose.Conclusions: CALMs vary in pigment intensity not only across individuals, but also within individuals and this variability was unrelated to sun exposure. Further studies may help elucidate the molecular basis of this finding, leading to an increased understanding of the pathogenesis of CALMs in NF1. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the contribution of European genetic admixture (EUADM) to insulin resistance syndrome (IRS) in a multiethnic sample of children age 7-12 years, and to explore whether body fat affects this relationship. Study design: Anthropometric measurements and blood pressure were assessed in 243 children. After an overnight fast, an intravenous glucose tolerance test was conducted, and measures of fasting insulin/glucose, lipids, insulin sensitivity (SI), and acute insulin response to glucose (AIRg) were obtained. The proportion of EUADM was determined by maximum likelihood estimation using 140 ancestry informative markers. Subjects were stratified into tertiles according to the proportion of EUADM for analyses. Subjects were categorized as lean or obese using body fat percentage cutpoints (25% in boys, 30% in girls). Results: Among lean subjects (72%), the tertile representing the greatest proportion of EUADM was associated with higher SI (P <.001) and serum glucose (P <.05) and lower insulin (P <.05), AIRg (P <.001), high-density lipoprotein cholesterol (P = .05), and blood pressure (P <.05). However, among obese subjects, EUADM was associated only with SI (P <.05). Conclusions: Our results suggest that population differences in IRS likely have a genetic component, but that the influence of genetic background may be masked by obesity. [Copyright &y& Elsevier]