10.1111/acn.v9999.9999

Vollständiger Abstract

Worum geht es in dieser Arbeit?

We describe a family with 11 members affected by oral, facial and digital findings, as well as adult-onset multiple long bone insufficiency fractures mimicking atypical femur fractures (AFF) on radiographs. The analysis of the pedigree of this family suggested an X-linked dominant inheritance. We performed whole-exome sequencing in this family. A rare novel variant, p.Ala642Asp (NM_003611, c.1925C>A, hg19) of the OFD1 gene was the only candidate on the X chromosome segregating with the phenotype within the family. The OFD1 gene targeted sequencing was carried out on 49 patients with AFF and 100 healthy controls. We detected another rare variant, p.Lys668Asn (NM_003611, c.2004G>C, hg19) of the OFD1 gene, in a woman with AFF. The structure of OFD1 protein has been predicted by AlphaFold 3 (AF3). According to the AF3 model of OFD1, the destabilization of the dimerization of OFD1 by the p.Ala642Asp variant and the breaking of ionic bond by the p.Lys668Asn variant could be pathogenic. This family demonstrates that such insufficiency fractures of long bones may occur in patients with oral-facial-digital syndrome and provides novel insight into the pathophysiology of these fractures and their association with dental and facial hypoplasia.

Abstract: PubMed · Datensatz