Analysis of the SPATA7 Gene in Patients With Leber Congenital Amaurosis and Childhood Onset Retinal Dystrophy

Abstract

Purpose: : To investigate the prevalence of sequence variants in SPATA7 in DNA from patients with Leber Congenital Amaurosis (LCA) and autosomal recessive severe childhood onset retinal dystrophy.

Methods: : Patients underwent standard ophthalmic evaluation including, where possible, perimetry, keratometry, electro-retinography, autofluorescence imaging and optical coherence tomography. 142 DNA samples from patients with LCA and autosomal recessive severe childhood onset rod cone dystrophy were previously analysed for mutations using a microarray (Asper-Ophthalmics LCA Chip) with negative results. The entire SPATA7 coding sequence was assayed, including the intron/exon junctions using a combination of direct DNA sequencing and Light Scanner high resolution melting analysis (Idaho technology). Identified mutations were confirmed by segregation analysis and novel changes screened in ethnically matched controls.

Results: : Screening of SPATA7 identified a number of known and novel SNPs. 3 unrelated patients (two of Pakistani ethnicity from consanguineous families, one British Caucasian without consanguinity) were identified to have coding changes. Mutations were homozygous in the consanguineous families while the third patient was a compound heterozygote. All three presented with severely reduced vision and nystagmus from birth or within the first 2 months of life. Mean visual acuity measured 2.14 logMAR right and 2.55 logMAR left eyes. One patient had keratoconus and was pseudophakic. All three had severe retinal degeneration with two showing scattered white dots in the periphery and arteriolar attenuation. Where possible, segregation analysis within the patient’s family showed that the mutations segregated with disease. Novel mutations were not found in 100 ECACC/ethnically matched controls.

Conclusions: : Mutations in SPATA7 are a rare cause of childhood retinal dystrophy accounting for 2% of disease in this cohort. The phenotype is of a severe retinal dystrophy.

Keywords: mutations • retinal degenerations: hereditary • gene screening