NovelTULP1Mutation Causing Leber Congenital Amaurosis or Early Onset Retinal Degeneration

Abstract

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.

TULP1Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones

“…7 From 2000 to the present day, approximately half of the published studies diagnose patients with TULP1 mutations as having LCA or EORD. [8][9][10][11][12][13][62][63][64] The remainder categorize the disease as arRP, but note childhoodonset vision loss and night blindness. 14,62,[65][66][67][68] Regardless of clinical diagnosis, early-onset night blindness, visual acuity loss and nystagmus are common findings.…”

“…[2][3][4][5][6] This was followed by reports of patients with TULP1 mutations and clinical descriptions that continued to describe the disease as arRP or used alternative diagnoses such as early-onset retinal degeneration (EORD) or Leber congenital amaurosis (LCA). [7][8][9][10][11][12][13][14][15] What do we know about retinal disease mechanisms in TULP1 deficiency? The tulp1 knockout mouse (tulp1 À/À ) shows progressive loss of rod and cone photoreceptor nuclei over the first 4 to 5 months of life.…”

Combining gene mapping and phenotype assessment for fast mutation finding in non-consanguineous autosomal recessive retinitis pigmentosa families

“…Today, 24 pathogenic variants have been described in TULP1, including 12 missense and 12 nonsense or frameshift mutations. [17][18][19][20][21][22][23][24][25][26][27] In all, 10 out of the 12 missense mutations are present in the tubby domain. The two novel missense mutations, R311Q and R342Q, that we have found in this study also affect amino acids of the tubby domain.…”

Reflectivity of the Outer Retina on Spectral-Domain Optical Coherence Tomography as a Predictor of Photoreceptor Cone Density

“…[6][7][8][9][10] However, a few authors performed experimental quantifications based on A-scans and underlined the potential benefit of this approach in predicting visual outcomes. [11][12][13][14] Even if the current OCT devices produce images of ocular tissue microstructure with up to 4 mm axial resolution, 15 they lack the lateral resolution necessary to image single retinal cells. A new imaging modality, adaptive optics, based on the correction of the optical aberrations of the eye, has contributed new insight into the retinal imaging field by providing real-time images of the macular photoreceptors with a resolution close to histology.…”