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#polysyndactyly

2 public questions tagged with this topic.

Limb Development -lll

Which mutation leads to human polysyndactyly (fusion of extra digits)?

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.

Ref: Muragaki et al., Science 1996, Gilbert Chapter 20: HoxD13 mutations and synpolydactyly.

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Tetrapod

Which HOX gene mutation is associated with human polysyndactyly (fusion of extra digits)?

HOXD13 is distal HoxA/D cluster member essential for autopod patterning, digit number, joint and interdigital separation. Polyalanine tract expansions, missense mutations altering homeodomain DNA binding disrupt downstream targets regulating BMP antagonism, interdigital apoptosis, and chondrogenic condensations. Resulting phenotype is synpolydactyly characterized by duplication and fusion of central digits, often with syndactyly. Mouse Hoxd13 knockouts show similar autopod defects, human pedigrees exhibit autosomal dominant inheritance with variable expressivity, confirming dosage-sensitive requirement of this transcription factor in distal limb morphogenesis and digit specification.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: HOXD13 mutation and human synpolydactyly.

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