54. Human polysyndactyly (joining of extra digits) syndrome results from a homozygous mutation at
    (1) antennapedia complex locus
    (2) one of the genes of Hox D
    (3) one of the genes of Hox C
    (4) β-catenin locus

Polysyndactyly, a condition characterized by the presence of extra digits (polydactyly) that are often fused (syndactyly), is usually caused by genetic mutations affecting limb development pathways. Among the critical genetic contributors are the homeobox gene clusters, especially the HOXD genes, which regulate the formation and patterning of digits during embryogenesis.

The Role of HOXD Genes in Limb Development

• The HOXD gene cluster, including the well-studied HOXD13 gene, encodes transcription factors essential for specifying positional information in the developing limb, particularly in the autopod (the distal part of the limb where fingers and toes form).

• Normal expression and function of HOXD genes are vital for specifying digit identity, number, and separation. Mutations lead to aberrations such as extra digits, fused digits, or malformed digits.

HOXD Gene Mutations and Polysyndactyly

• Human polysyndactyly syndrome has been linked to homozygous or heterozygous mutations in HOXD genes, primarily affecting HOXD13.

• These mutations alter transcription factor function, disrupting gene regulatory networks that establish digit boundaries and cause digit malformations.

• The syndrome manifests clinically as additional fingers or toes that are often fused, reflecting disturbed morphogenesis during limb patterning.

Why Other Genetic Loci Are Less Relevant

• Antennapedia complex locus (option 1) is related to fly development and not implicated in human limb malformations.

• HOXC genes (option 3) mainly regulate more proximal limb and trunk structures rather than distal digit patterning.

• β-catenin (option 4) is a part of the Wnt signaling pathway affecting various developmental processes but is not the primary genetic locus for polysyndactyly.

Summary

Human polysyndactyly, featuring extra and often fused digits, is most commonly linked to mutations in the HOXD gene cluster, particularly the HOXD13 gene. These mutations disrupt the positional coding and morphogenetic events governing digit formation, leading to common congenital limb anomalies.

Final Answer:
(2) one of the genes of Hox D