title: Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects.
abstract: The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/β-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression.
authors: Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK.
authors: Kamron
authors: K
authors: Khan
authors: Clare V
authors: CV
authors: Logan
authors: Martin
authors: M
authors: McKibbin
authors: Eamonn
authors: E
authors: Sheridan
authors: Nursel H
authors: NH
authors: Elçioglu
authors: Ozlem
authors: O
authors: Yenice
authors: David A
authors: DA
authors: Parry
authors: Narcis
authors: N
authors: Fernandez-Fuentes
authors: Zakia I A
authors: ZI
authors: Abdelhamed
authors: Ahmed
authors: A
authors: Al-Maskari
authors: James A
authors: JA
authors: Poulter
authors: Moin D
authors: MD
authors: Mohamed
authors: Ian M
authors: IM
authors: Carr
authors: Joanne E
authors: JE
authors: Morgan
authors: Hussain
authors: H
authors: Jafri
authors: Yasmin
authors: Y
authors: Raashid
authors: Graham R
authors: GR
authors: Taylor
authors: Colin A
authors: CA
authors: Johnson
authors: Chris F
authors: CF
authors: Inglehearn
authors: Carmel
authors: C
authors: Toomes
authors: Manir
authors: M
authors: Ali
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis / Q000379:methods*; D005123:Eye / Q000196:embryology* / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics / Q000473:pathology; D005128:Eye Diseases / Q000235:genetics* / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012160:Retina / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D051176:beta Catenin; C456975:ATOH7 protein, human; C081848:NDP protein, human