Family-based whole-exome sequencing implicates a variant in lysyl oxidase like 4 in atypical femur fractures.

ABSTRACT: Atypical femur fractures (AFFs) are rare adverse events associated with bisphosphonate use, having unclear pathophysiology. AFFs also cluster in families and have occurred in patients with monogenetic bone diseases sometimes without bisphosphonate use, suggesting an underlying genetic susceptibility. Our aim was to identify a genetic cause for AFF in a Caucasian family with 7 members affected by osteoporosis, including 3 siblings with bisphosphonate-associated AFFs. Using whole-exome sequencing, we identified a rare pathogenic variant c.G1063A (p.Gly355Ser) in lysyl oxidase like 4 (LOXL4) among 64 heterozygous rare, protein-altering variants shared by the 3 siblings with AFFs. The same variant was also found in a fourth sibling with a low-trauma femur fracture above the knee, not fulfillin

SUBMITTER: Zhou W 

PROVIDER: S-EPMC11700580 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature