Background: Brachydactyly A1 (BDA1) is an autosomal dominant disorder. It manifests as shortness/absence of the middle phalanges in the hands and feet. It is caused by a variation in the Indian hedgehog (IHH) gene. The IHH gene plays an important role in the development of limbs. IHH is expressed in the pre-hypertrophic chondrocytes of cartilage elements, where it regulates the rate of hypertrophic differentiation. A lack of IHH prevents proliferating chondrocytes from initiating the hypertrophic differentiation process. This study aimed to identify IHH gene variants in BDA1 individuals.
Methods: The present study used Sanger sequencing to analyze IHH variants in three exons and in silico tools for detailed variant analysis.
Results: A total of 44 individuals were sequenced - 14 BDA1 individuals and 30 healthy controls. Sanger sequencing revealed a novel variant in the IHH gene in exon 1 and exon 2. A variant was found to segregate affected individuals in a family.
Conclusion: The present study findings further expand the mutation spectrum of the IHH gene, and provide detailed mutant protein changes by in silico methods. The study also provides additional evidence that IHH plays an important role in limb development and short stature.
Key words: Brachydactyly, missense, Indian hedgehog, phalanges, metacarpals, metatarsals, Sanger sequencing, short hands.
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