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Genetic basis of hyperostosis cranialis interna



DOI:10.1038/bonekey.2013.166

Hyperostosis cranialis interna (HCI), first described in 1990, is an extremely rare genetic disorder. It is autosomal dominant and causes severe malformation of the calvaria and skull base, leaving the rest of the skeleton unscathed.

HCI is known in only three families worldwide. This Dutch group all share the same ancestry, suggesting that the mutation responsible occurred around five generations ago. In this study, Borra et al. performed a linkage analysis using DNA samples from members of this extended family and have identified a potential candidate gene on chromosome 8p21.

The gene occurs within the region between two markers, D8S282 and D8S382, and possible candidates are LOXL2 (encoding lysyl oxidase 2), BMP1 (encoding bone morphogenetic protein 1) and ADAM28 (encoding a disintegrin and metalloprotease domain 28). However, when the sequences of all three genes were analysed in the samples, no obvious mutations were uncovered. The authors then carried out an analysis of single nucleotide polymorphisms in the region and ruled out major deletions; both copies of each gene were definitely present.

Editor’s comment: Exome sequencing of 8p21 should be considered as an important next step in this research; there are still many genes in this region, including plenty not previously suspected of having any involvement in sclerosing bone dysplasia.


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