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M. H. Tan, H. V. Tran, A. J. Smith, R. Henderson, I. Russell-Eggitt, A. G. Robson, A. R. Webster, G. E. Holder, R. R. Ali, A. T. Moore; Clinical Spectrum of Patients With AIPL1 Mutations in Recessive Inherited Retinal Dystrophies. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3087.
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© ARVO (1962-2015); The Authors (2016-present)
To report the spectrum of clinical phenotype and genotype associated with Lebers Congenial Amaurosis (LCA) and autosomal recessive childhood onset retinal dystrophy caused by AIPL1 sequence variants in a single institution.
A total of 292 unrelated probands with LCA or childhood onset autosomal recessive retinal dystrophy were screened for mutations in AIPL1 using a combination of microarray LCA chip analysis (Asper-Ophthalmics) and bidirectional sequencing of 6 exons including splice donor and acceptor sites. The results of clinical evaluation, electrophysiology (ERG) and imaging were reviewed.
Seven homozygotes and 12 compound heterozygotes were identified. Of the compound heterozygotes, 8 patients had novel sequence variants. The age of patients at time of onset of symptoms ranged from birth to 48 months (mean age of onset=9.8+/-3.5 months [SEM]). Visual acuities ranged from no light perception to logMar 0.12.Thirteen patients (68%) presented with nystagmus. Nyctalopia was present in 10 (53%). Fundus appearance ranged from near-normal appearance to variable degrees of chorioretinal atrophy and peripheral bone-spicule pigmentation. White dots at the level of the retinal pigment epithelium were seen in 9 (42%) patients. Macular atrophy was present in 10 (53%), mostly in patients with homozygous or null mutations. OCT analysis showed variable retinal thinning. Goldman perimetry showed severe constriction. In 5 patients tested according to International Standards, rod ERG was undetectable in 7 of 10 eyes and markedly subnormal in 3 eyes of 2 subjects. Bright flash ERG a-waves were undetectable in 5 of 10 eyes and subnormal in the others. In the 3 subjects with detectable 30Hz flicker ERGs, waveforms were markedly delayed and reduced. In 4 individuals tested with surface peri-orbital electrodes, ERGs were undetectable or subnormal consistent with generalized cone and rod system dysfunction.
Mutations in the AIPL1 gene result in a spectrum of phenotypes. Null mutations are more likely to be associated with severe retinal disease and maculopathy.
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