Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome.

@article{Twigg2004MutationsOE,
  title={Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome.},
  author={Stephen R F Twigg and Rui Kan and Christian Babbs and Elena G. Bochukova and Stephen P. Robertson and Steven Arthur Wall and Gillian M. Morriss-Kay and Andrew O. M. Wilkie},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2004},
  volume={101 23},
  pages={
          8652-7
        }
}
  • S. Twigg, R. Kan, A. Wilkie
  • Published 8 June 2004
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
Craniofrontonasal syndrome (CFNS) is an X-linked developmental disorder that shows paradoxically greater severity in heterozygous females than in hemizygous males. Females have frontonasal dysplasia and coronal craniosynostosis (fusion of the coronal sutures); in males, hypertelorism is the only typical manifestation. Here, we show that the classical female CFNS phenotype is caused by heterozygous loss-of-function mutations in EFNB1, which encodes a member of the ephrin family of transmembrane… 

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Ephrin-B1 Regulation of Cell Positioning in Craniofacial Development and Congenital Disease

TLDR
Using mouse models and the first human induced pluripotent stem cell model of a human craniofacial disease, it is established that ephrin-B1 mosaicism drives pathogenic cell segregation in human cell types relevant to CFNS and that e phrin- B1 is a potent regulator of segregation not only in the early neuroepithelium, but also in the craniafacial mesenchyme, correlating with dysmorphology of facial structures.

Molecular Analysis of Ephrin A4 and Ephrin B1 in a Rabbit Model of Craniosynostosis

TLDR
Data indicate that the causal locus for heritable CS in this rabbit model is not located within the structural coding regions of either EFNA4 or EFNB1, indicating that the genetic basis for synostosis within this model remains unknown.

Aberrant cell segregation in the craniofacial primordium and the emergence of facial dysmorphology in craniofrontonasal syndrome

TLDR
It is found that EPHRIN-B1 regulates cell segregation independently in early neural development and later in craniofacial development, correlating with the emergence of quantitative differences in face shape, which advances the understanding of the etiology and signaling interactions underlying CFNS dysmorphology.

The impact of CFNS-causing EFNB1 mutations on ephrin-B1 function

TLDR
Pathogenic mechanisms in CFNS manifestation include impaired ephrin-B1 signalling combined with cellular interference, and missense mutations located in the extracellular ephrine domain involved in Eph-ephrin-B 1 recognition and higher order complex formation are studied.

A Novel Mutation in EFNB1, Probably with a Dominant Negative Effect, Underlying Craniofrontonasal Syndrome

TLDR
A Thai woman with CFNS is reported, in whom a novel mutation was discovered: c.685_686insG, in exon 5 of EFNB1, which is the first insertion and the most 3′ point mutation inEFNB1 reported to date.

Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes

TLDR
A more severe outcome in mosaic is demonstrated than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females.

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

TLDR
It is proposed that X‐linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin‐B1 leads to craniofacial abnormalities.

Dissecting the molecular mechanisms in craniofrontonasal syndrome: differential mRNA expression of mutant EFNB1 and the cellular mosaic

TLDR
Expression of EFNB1 mRNA was studied by RT-PCR in fibroblast cultures established from CFNS female patients to suggest differential degradation of mutant EF NB1 transcripts by the nonsense-mediated mRNA decay pathway, further supporting the concept of cellular interference in CFNS.

Aberrant cell segregation in craniofacial primordia and the emergence of facial dysmorphology in craniofrontonasal syndrome

TLDR
It is found that ephrin-B1 regulates cell segregation independently in early neural development and later in craniofacial development, correlating with the emergence of quantitative differences in face shape, which advances the understanding of the morphogenetic etiology and signaling interactions underlying CFNS dysmorphology.

Twenty‐six novel EFNB1 mutations in familial and sporadic craniofrontonasal syndrome (CFNS)

TLDR
It is concluded that the major causes of familial as well as sporadic CFNS are loss of function mutations in the EFNB1 gene that comprise premature termination or abrogate receptor‐ligand interaction, oligomerization, and ephrin‐B1 reverse signaling.
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