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Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Changes in the Appendicular Skeleton with Age01:09

Changes in the Appendicular Skeleton with Age

The upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after.
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Development of the Limb Synovial Joints01:07

Development of the Limb Synovial Joints

Joints form during embryonic development in conjunction with the formation and growth of the associated bones. The embryonic tissue that gives rise to all bones, cartilage, and connective tissues of the body is called mesenchyme.
The mesenchymal stem cells differentiate into chondrocytes that form the hyaline cartilage, and later the cartilaginous model of the bone. This model further transforms into a bone. This process is known as endochondral ossification.
During development, the limbs...

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Related Experiment Video

Updated: Jul 24, 2026

Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis
07:40

Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis

Published on: January 4, 2017

Limb malformations and the human HOX genes.

Frances R Goodman1

  • 1Molecular Medicine Unit, Institute of Child Health, London, England. fgoodman@hgmp.mrc.ac.uk

American Journal of Medical Genetics
|October 3, 2002
PubMed
Summary

Mutations in HOXA13 and HOXD13 genes cause various limb malformations, including synpolydactyly and hand-foot-genital syndrome. These genetic changes lead to unpredictable developmental issues beyond mouse models.

Area of Science:

  • Developmental Biology
  • Human Genetics
  • Molecular Biology

Background:

  • HOX genes are crucial transcription factors for embryonic development and body patterning.
  • Humans possess 39 HOX genes in four clusters, vital for developing numerous organ systems and limbs.
  • Synpolydactyly and hand-foot-genital syndrome were the first limb malformations linked to human HOX gene mutations (HOXD13 and HOXA13, respectively).

Purpose of the Study:

  • To review diverse limb malformations caused by specific mutations in HOXA13 and HOXD13.
  • To highlight how mutations like polyalanine expansions, nonsense, and missense mutations lead to limb defects.
  • To discuss limb malformations arising from chromosomal deletions or regulatory mutations affecting HOX gene clusters.

Main Methods:

  • Literature review of studies on HOX gene mutations and associated limb malformations.

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Last Updated: Jul 24, 2026

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07:40

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Published on: January 4, 2017

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  • Analysis of mutation types (polyalanine tract expansions, nonsense, missense) in HOXA13 and HOXD13.
  • Examination of limb malformations resulting from chromosomal deletions and regulatory mutations impacting HOX genes.

    • Main Results:

    • Specific mutations in HOXD13 and HOXA13 cause a range of limb malformations, including synpolydactyly and hand-foot-genital syndrome.
    • Phenotypic outcomes of these mutations are often unpredictable and differ from findings in mouse models.
    • Chromosomal deletions within HOXD and HOXA clusters, and regulatory mutations, also contribute to limb malformations.

    Conclusions:

    • HOXA13 and HOXD13 gene mutations are significant causes of human limb malformations.
    • Understanding these mutations is critical for diagnosing and potentially treating congenital limb defects.
    • Further research is needed to fully elucidate the genotype-phenotype correlations and mechanisms underlying HOX-related limb malformations.