Duplication of the EFNB1 Gene in Familial Hypertelorism: Imbalance in Ephrin-B1 Expression and Abnormal Phenotypes in Humans and Mice
2011

Duplication of the EFNB1 Gene in Familial Hypertelorism

Sample size: 3 publication 10 minutes Evidence: moderate

Author Information

Author(s): Babbs Christian, Stewart Helen S, Williams Louise J, Connell Lyndsey, Goriely Anne, Twigg Stephen RF, Smith Kim, Lester Tracy, Wilkie Andrew OM

Primary Institution: Weatherall Institute of Molecular Medicine, University of Oxford

Hypothesis

The difference in expression level of EFNB1 due to X-inactivation results in abnormal cell sorting leading to hypertelorism.

Conclusion

The study suggests that a duplication of the EFNB1 gene is likely responsible for hypertelorism in the studied family.

Supporting Evidence

  • The X chromosome with the duplication produces approximately 1.6-fold more EFNB1 transcript than the normal X chromosome.
  • Evidence from a mouse model shows that abnormal cell sorting occurs in the cranial region.
  • The duplication of EFNB1 segregates with the hypertelorism phenotype in the family.

Takeaway

Some people in a family have widely spaced eyes because they have an extra piece of DNA that makes a gene work too much.

Methodology

DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to analyze the EFNB1 gene and its expression levels.

Limitations

The study does not exclude the potential contributions of other duplicated genes in the observed phenotypes.

Participant Demographics

The study involved a family with a history of hypertelorism across three generations.

Digital Object Identifier (DOI)

10.1002/humu.21521

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