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The molecular genetics of human appendicular skeleton

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Abstract

Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of “Nosology and Classification of Genetic skeletal disorders: 2019 Revision”. In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand–foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand–foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.

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Acknowledgements

We are thankful to our lab members for their valuable suggestions and help in finding relevant literature.

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  1. Gomal Centre of Biochemistry and Biotechnology, Gomal University, Indus Highway, Multan Road, Dera Ismail Khan, 29050, Khyber Pakhtunkhwa, Pakistan

    Safeer Ahmad, Muhammad Zeeshan Ali, Muhammad Muzammal & Muzammil Ahmad Khan

  2. Translational Research Institute & Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar

    Fayaz Ahmad Mir

  3. Department of Human Genetics, Sidra Medical and Research Centre, Doha, Qatar

    Muzammil Ahmad Khan

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SA, MZA and MM have gathered all the scientific information and classified them. FAM helped in technical review and improvement of manuscript language. MAK conceptualized and supervised the data analysis, interpretation and manuscript drafting. All the authors have read, edited and approved the final version of manuscript.

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Ahmad, S., Ali, M.Z., Muzammal, M. et al. The molecular genetics of human appendicular skeleton. Mol Genet Genomics 297, 1195–1214 (2022). https://doi.org/10.1007/s00438-022-01930-1

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