| Popis: |
Background Developmental dysplasia of the hip (DDH) is a common condition involving instability of the hip with multifactorial etiology. Early diagnosis and treatment are critical as undetected DDH is an important cause of long-term hip complications. Better diagnostics may be achieved through genetic methods, especially for patients with positive family history. Several candidate genes have been reported but the exact molecular etiology of the disease is yet unknown. Results In the present study, we performed whole exome sequencing of DDH patients from 29 families with at least two affected first-degree relatives. We identified PPP6R2 as a novel DDH gene as two rare missense mutations were identified in three families co-segregating with disease. Mutational burden analysis across the families identified 455 candidate genes, with many genes involved in mechanotransduction, in particular the cilia, the cytoskeleton, the extracellular matrix, and the Notch pathway. ConclusionsHere we report for the first time a previously uncorrelated gene with DDH, PPP6R2. Taken altogether, the data suggest a polygenic mode of inheritance for DDH, and we propose that impaired mechanotransduction is involved in the etiopathological mechanism. |
