Mutation In Fkbp10 Gene Cause Bruck Syndrome 1 (Brks1) In A Pakistani Family Of Pashtun Origin

Area of Science:

• Genetics and Molecular Biology
• Pediatrics
• Rare Diseases

Background:

• Bruck syndrome 1 (BRKS1) is an exceptionally rare genetic disorder characterized by infantile fractures, joint contractures, short stature, limb deformities, and scoliosis.
• Fewer than fifty cases of BRKS1 have been documented globally, highlighting its rarity.

Observation:

• This report presents two siblings from a consanguineous Pashtun family in Karachi diagnosed with Bruck syndrome 1.
• The cases exhibited recurrent fractures, limb deformities, reduced bone mineral density, arthrogryposis multiplex congenita, and polydactyly.

Findings:

• Genetic analysis revealed both siblings were homozygous for the pathogenic FKBP10 gene variant c.344G>A (p.Arg115Gln), confirming the BRKS1 diagnosis.
• This study reports the FKBP10 mutation in the Pakistani Pashtun population for the first time.
• Post-axial polydactyly and spina bifida were observed in association with the FKBP10 mutation, marking a novel finding.

Implications:

• This research expands the known clinical spectrum of FKBP10 mutations.
• It provides crucial insights into BRKS1 in a previously unreported ethnic group.
• Detailed skeletal surveys aid in understanding the disease's phenotypic variability.