|Title||Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Oh, Jin Kyun, Del Valle José G. Vargas, de Carvalho Jose Ronaldo Li, Sun Young Joo, Levi Sarah R., Ryu Joseph, Yang Jing, Nagasaki Takayuki, Emanuelli Andres, Rasool Nailyn, Allikmets Rando, Sparrow Janet R., Izquierdo Natalio J., Duncan Jacque L., Mahajan Vinit B., and Tsang Stephen H.|
|Journal||Orphanet J Rare Dis|
|Date Published||2022 04 01|
|Keywords||Carrier Proteins, Electroretinography, Genetic Association Studies, Humans, Mutation, Phenotype, Retinal Dystrophies|
BACKGROUND: Inherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5. Examination of these patients included funduscopic evaluation, spectral-domain optical coherence tomography, short-wavelength autofluorescence, and full-field electroretinography (ffERG). Genetic diagnoses were confirmed using whole exome capture. Protein modeling of the identified variants was performed to explore potential genotype-phenotype correlations.
RESULTS: Genetic testing revealed five novel variants in TTLL5 in three unrelated patients with retinal dystrophy. Clinical imaging demonstrated features of sectoral cone-rod dystrophy and cone dystrophy, with phenotypic variability seen across all three patients. One patient also developed high-frequency hearing loss during a similar time period as the onset of retinal disease, potentially suggestive of a syndromic disorder. Retinal structure findings were corroborated with functional measures including ffERG findings that supported these diagnoses. Modeling of the five variants suggest that they cause different effects on protein function, providing a potential reason for genotype-phenotype correlation in these patients.
CONCLUSIONS: The authors report retinal phenotypic findings in three unrelated patients with novel mutations causing autosomal recessive TTLL5-mediated retinal dystrophy. These findings broaden the understanding of the phenotypes associated with TTLL5-mediated retinal disease and suggest that mutations in TTLL5 should be considered as a potential cause of sectoral retinal dystrophy in addition to cone-rod and cone dystrophies.
|Alternate Journal||Orphanet J Rare Dis|
|PubMed Central ID||PMC8973795|
|Grant List||R24 EY027285 / EY / NEI NIH HHS / United States |
R01 EY018213 / EY / NEI NIH HHS / United States
P30 EY026877 / EY / NEI NIH HHS / United States
R01 EY024698 / EY / NEI NIH HHS / United States
P30 CA013696 / CA / NCI NIH HHS / United States
R01 EY026682 / EY / NEI NIH HHS / United States
R01 EY028203 / EY / NEI NIH HHS / United States
R21 AG050437 / AG / NIA NIH HHS / United States
P30 EY019007 / EY / NEI NIH HHS / United States
U01 EY030580 / EY / NEI NIH HHS / United States
P30 EY002162 / EY / NEI NIH HHS / United States