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Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, frequently associated with reduced bone mineral density. Serum 25-hydroxyvitamin D3 concentrations in NF1 adults are lower than in healthy controls in autumn respectively winter and are inversely correlated with the number of dermal neurofibromas. We investigated 25-hydroxyvitamin D3 levels in children and adults with neurofibromatosis type 1 in winter and summer and compared them to healthy controls to get more pathogenic insights in vitamin D3 metabolism in NF1 patients., Design and Methods: NF1 patients were clinically examined and serum 25-hydroxyvitamin D3 concentrations were measured in 58 NF1 adults and 46 children in winter as well as in summer and compared to sex-, age- and month-matched controls., Results: 52 adults suffered from 10 to 5000 dermal neurofibromas, whereas none of the children presented neurofibromas. 25-Hydroxyvitamin D3 increased from winter to summer (mean: 21.0 to 46.5nmol/l) in NF1 adults. This increase was even larger (p=0.0001) than in healthy controls (mean: 50.5 to 60.5nmol/l). However, there were no differences of 25-hydroxyvitamin D3 concentrations in NF1 children and healthy controls both in winter and in summer., Conclusions: Only adults with NF1 showed lower 25-hydroxyvitamin D3 levels in winter and summer, which are unlikely due to impaired UV-dependent dermal synthesis, but rather might be caused by an accelerated catabolism., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

We performed a family-based association study to test the hypothesis that genetic variation at the human orthologue of the mouse progressive ankylosis gene (ANKH) is involved in determining bone size (BS) and bone geometry (BG). The study population comprised 126 nuclear families with 574 adult Chuvashian individuals living in small villages in the Russian Federation. Quantitative bone traits were determined by analyzing plain hand radiographs. Familial correlations for all studied traits revealed a high degree of heritability in this ethnically homogeneous population. Three simple tandem repeat (STR) polymorphisms, one intragenic and two flanking markers, as well as six single nucleotide polymorphisms (SNPs) were tested. The SNPs were detected by re-sequencing experiments and covered ANKH exons with their flanking splice sites and the promoter region. We used three different transmission disequilibrium tests (TDTs) and obtained multiple significant association signals for all investigated bone traits. Alleles of several markers located at different positions of the ANKH locus, including the promoter, consistently revealed the association. The bone traits tested are closely related to bone fragility suggesting a role for ANKH in osteoporosis.