title: Screening of SPATA7 in patients with Leber congenital amaurosis and severe childhood-onset retinal dystrophy reveals disease-causing mutations.
abstract: OBJECTIVE
  To investigate the prevalence of sequence variants in the gene SPATA7 in patients with Leber congenital amaurosis (LCA) and autosomal recessive, severe, early-onset retinal dystrophy (EORD) and to delineate the ocular phenotype associated with SPATA7 mutations.
  
  
  METHODS
  Patients underwent standard ophthalmic evaluation after providing informed consent. One hundred forty-one DNA samples from patients with LCA and EORD had been analyzed for mutations by using a microarray, with negative results. One additional patient underwent SPATA7 screening due to a region of autozygosity surrounding this gene. A further patient was screened who had a compatible ocular phenotype. The entire SPATA7 coding sequence was assayed, including the intron-exon junctions, by using a combination of direct DNA sequencing and high-resolution melting screening.
  
  
  RESULTS
  Screening of SPATA7 identified several known and novel single-nucleotide polymorphisms (SNPs). Affected individuals from five unrelated families were identified to have coding changes. Clinical features demonstrated a severe infantile onset retinal dystrophy, similar to Leber congenital amaurosis. The retina had widespread retinal pigment epithelial atrophy, with minimal pigment migration into the neurosensory retina. Fundus autofluorescence imaging showed a parafoveal annulus of increased autofluorescence. High-definition optical coherence tomography showed preservation of the inner segment/outer segment junction at the fovea.
  
  
  CONCLUSIONS
  Mutations in SPATA7 are a rare cause of childhood retinal dystrophy accounting for 1.7% of disease in this cohort. Affected patients present in infancy with severe visual loss, but may have some preservation of the photoreceptor structure in the central retina.
authors.affiliation: Department of Genetics, Institute of Ophthalmology, London, United Kingdom. d.mackay@ucl.ac.uk
authors.forename: Donna S
authors.initials: DS
authors.lastname: Mackay
authors.forename: Louise A
authors.initials: LA
authors.lastname: Ocaka
authors.forename: Arundhati Dev
authors.initials: AD
authors.lastname: Borman
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.forename: Robert H
authors.initials: RH
authors.lastname: Henderson
authors.forename: Phillip
authors.initials: P
authors.lastname: Moradi
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Thompson
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005820:Genetic Testing; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D058499:Retinal Dystrophies / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics*; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C482323:SPATA7 protein, human