Rare Novel Genetic Variants of the OFD1 Gene Associated With a Familial Form and a Sporadic Case of Long Bone Atypical Fractures.
Marie-Ève Boisvert, Halim Maaroufi, Rachel Laframboise et al.
✦ AI-curated · Sources linked
Case in brief
A family with 11 affected members had oral, facial and digital findings, together with adult-onset multiple long-bone insufficiency fractures that resembled atypical femur fractures on radiographs. Pedigree analysis suggested X-linked dominant inheritance. Whole-exome sequencing identified an OFD1 variant, p.Ala642Asp, as the only X-chromosomal candidate segregating with the family phenotype. Targeted OFD1 sequencing in 49 patients with atypical femur fractures and 100 healthy controls found a second rare OFD1 variant, p.Lys668Asn, in a woman with atypical femur fractures. Protein modelling suggested possible effects on OFD1 structure for both variants.
What made this case unusual
The family’s adult-onset long-bone insufficiency fractures mimicked atypical femur fractures and occurred alongside oral-facial-digital findings, linking this phenotype with OFD1 variants.
Diagnostic / clinical pearl
In patients with oral-facial-digital findings and atypical long-bone insufficiency fractures, consider whether the fracture phenotype may be part of an OFD1-associated syndrome.
Why it matters
The report broadens the described phenotype associated with OFD1 and suggests a possible connection between long-bone fractures and dental and facial hypoplasia.