Practice question

Human synpolydactyly type II results from HoxD13 polyalanine tract expansion mutations within N-terminal coding region affecting transcription. HoxD13 normally patterns distal autopod, regulates digit number, length and interdigital separation by modulating BMP antagonists and Ephrin signaling at digit tips. Expanded tract causes protein aggregation, dominant negative interference with other Hox13 proteins, leading to defective interdigital BMP signaling, persistent soft-tissue webbing and extra fused digits with brachydactyly. TBX5 causes Holt-Oram syndrome, HoxA11 affects zeugopod, Lmx1b causes nail-patella syndrome. Hence HoxD13 links to polysyndactyly.