PHENOTYPIC VARIABILITY IN INDIVIDUALS WITH TYPE V OSTEOGENESIS IMPERFECTA WITH IDENTICAL IFITM5 MUTATIONS

Area of Science:

• Genetics
• Molecular Biology
• Skeletal Dysplasias

Background:

• Osteogenesis imperfecta (OI) type V is a rare genetic disorder affecting bone development.
• It is characterized by bone fragility, deformities, and specific forearm abnormalities.
• A mutation in the IFITM5 gene has been identified as the cause of OI type V.

Purpose of the Study:

• To investigate the genetic basis of OI type V in a diverse cohort.
• To characterize the phenotypic variability associated with the IFITM5 mutation.
• To confirm the role of the c.-14 IFITM5 variant in OI type V.

Main Methods:

• Sanger sequencing was used to identify the IFITM5 mutation.
• Exome sequencing was performed but did not identify the causative mutation.
• Clinical data and family history were collected for affected individuals.

Main Results:

• The c.-14 IFITM5 variant was identified in all affected individuals with OI type V.
• Phenotypic variability was observed both between and within families.
• The mutation results in an aberrant IFITM5 protein with an extended N-terminus.

Conclusions:

• The c.-14 IFITM5 mutation is the cause of OI type V.
• Significant clinical variability exists for OI type V, influenced by modifier genes.
• This study expands the known ethnic diversity of individuals affected by OI type V.