Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration.
OBJECTIVE
To report a large, consanguineous Algerian family affected with Leber congenital amaurosis (LCA) or early-onset retinal degeneration (EORD).


METHODS
All accessible family members underwent a complete ophthalmic examination, and blood was obtained for DNA extraction. Homozygosity mapping was performed with markers flanking 12 loci associated with LCA. The 15 exons of TULP1 were sequenced.


RESULTS
Seven of 30 examined family members were affected, including five with EORD and two with LCA. All patients had nystagmus, hemeralopia, mild myopia, and low visual acuity without photophobia. Fundus features were variable among EORD patients: typical spicular retinitis pigmentosa or clumped pigmented retinopathy with age-dependent macular involvement. A salt-and-pepper retinopathy with midperipheral retinal pigment epithelium (RPE) atrophy was present in the older patients with LCA, whereas the retina appeared virtually normal in the younger ones. Both scotopic and photopic electroretinograms were nondetectable. Fundus imaging revealed a perifoveal ring of increased fundus autofluorescence (FAF) in the proband, and optical coherence tomography disclosed a thinned retina, mainly due to photoreceptor loss. Linkage analysis identified a region of homozygosity on chromosome 6, region p21.3, and mutation screening revealed a novel 6-base in-frame duplication, in the TULP1 gene.


CONCLUSIONS
Mutation in the TULP1 gene is a rare cause of LCA/EORD, with only 14 mutations reported so far. The observed intrafamilial phenotypic variability could be attributed to disease progression or possibly modifier alleles. This study provides the first description of FAF and quantitative reflectivity profiles in TULP1-related retinopathy.
Mataftsi
Asimina
A
IRO (Institute of Research in Ophthalmology), Sion, Switzerland.
Schorderet
Daniel F
DF
Chachoua
Louisa
L
Boussalah
Myriam
M
Nouri
Mohamed T
MT
Barthelmes
Daniel
D
Borruat
François-Xavier
FX
Munier
Francis L
FL
D000328:Adult; D001766:Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020131:Genes, Duplicate / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009216:Myopia / Q000235:genetics; D020417:Nystagmus, Congenital / Q000235:genetics; D010375:Pedigree; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000235:genetics
D005136:Eye Proteins; C105443:TULP1 protein, human