Emma N Hilton

Publications (3)16.86 Total impact

• Source

  Available from: Geoffrey Maher

  Article: The cataract-associated protein TMEM114, and TMEM235, are glycosylated transmembrane proteins that are distinct from claudin family members.

  Geoffrey J Maher, Emma N Hilton, Jill E Urquhart, Alice E Davidson, Helen L Spencer, Graeme C Black, Forbes D Manson
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  ABSTRACT: A novel gene, TMEM114, was annotated as a member of the claudin gene family and was subsequently associated as a cause of autosomal dominant cataract because of a translocation in its putative promoter. Our bioinformatic and molecular analyses of TMEM114, and the closely related TMEM235, demonstrate that these proteins are more closely related to members of the voltage dependent calcium channel gamma subunit family. TMEM114 and TMEM235 differed from claudins in terms of localisation in polarised epithelial cells and by the presence of N-linked glycans. By gene expression knockdown in Xenopus tropicalis we also demonstrate a role for Tmem114 in eye development.
  FEBS letters 06/2011; 585(14):2187-92. · 3.54 Impact Factor
• Article: Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome.

  May Tassabehji, Zhi Ming Fang, Emma N Hilton, Julie McGaughran, Zhongming Zhao, Charles E de Bock, Emma Howard, Michael Malass, Dian Donnai, Ashish Diwan, Forbes D C Manson, Dédée Murrell, Raymond A Clarke
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  ABSTRACT: Klippel-Feil syndrome (KFS) is a congenital disorder of spinal segmentation distinguished by the bony fusion of anterior/cervical vertebrae. Scoliosis, mirror movements, otolaryngological, kidney, ocular, cranial, limb, and/or digit anomalies are often associated. Here we report mutations at the GDF6 gene locus in familial and sporadic cases of KFS including the recurrent missense mutation of an extremely conserved residue c.866T>C (p.Leu289Pro) in association with mirror movements and an inversion breakpoint downstream of the gene in association with carpal, tarsal, and vertebral fusions. GDF6 is expressed at the boundaries of the developing carpals, tarsals, and vertebrae and within the adult vertebral disc. GDF6 knockout mice are best distinguished by fusion of carpals and tarsals and GDF6 knockdown in Xenopus results in a high incidence of anterior axial defects consistent with a role for GDF6 in the etiology, diversity, and variability of KFS.
  Human Mutation 04/2008; 29(8):1017-27. · 5.69 Impact Factor
• Article: Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination.

  Emma N Hilton, Forbes D C Manson, Jill E Urquhart, Jennifer J Johnston, Anne M Slavotinek, Peter Hedera, Eva-Lena Stattin, Ann Nordgren, Leslie G Biesecker, Graeme C M Black
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  ABSTRACT: Oculofaciocardiodental (OFCD) syndrome is an X-linked male lethal condition encompassing cardiac septal defects, as well as ocular and dental anomalies. The gene mutated in OFCD syndrome, the BCL-6 corepressor (BCOR), is part of a transcriptional repression complex whose transcriptional targets remain largely unknown. We reviewed cases of OFCD syndrome and identified patients exhibiting defective lateralization including dextrocardia, asplenia and intestinal malrotation, suggesting that BCOR is required in normal laterality determination. To study the function of BCOR, we used morpholino oligonucleotides (MOs) to knockdown expression of xtBcor in Xenopus tropicalis, thus creating an animal model for OFCD syndrome. The resulting tadpoles had cardiac and ocular features characteristic of OFCD syndrome. Reversed cardiac orientation and disorganized gut patterning were seen when MOs were injected into the left side of embryos, demonstrating a left-sided requirement for xtBcor in lateral determination in Xenopus. Ocular defects displayed no left-right bias and included anterior and posterior segment disorders such as microphthalmia and coloboma. Expression of xtPitx2c was shown to be downregulated when xtBcor was depleted. This identifies a pathway in which xtBcor is required for lateral specification, a process intrinsically linked to correct cardiac septal development.
  Human Molecular Genetics 08/2007; 16(14):1773-82. · 7.64 Impact Factor