Pathogenic variants in
are associated with autosomal dominant retinitis pigmentosa 10 (RP10), and Leber congenital amaurosis 11. This case report of a 13-year-old girl with Down's syndrome and ...keratoglobus is aimed at linking the novel variant
c.134A>G, p.(Tyr45Cys), a variant of uncertain significance, to a clinical phenotype and to provide grounds for the objective assignment of its benign features. RP10 is characterized by the early onset and rapid progression of ocular symptoms, beginning with nyctalopia in childhood, accompanied by typical RP fundus changes. As evidenced via thorough clinical examination and testing, none of the RP10 characteristics were present in our patient. On the contrary, our patient who was heterozygous for
c.134A>G, p.(Tyr45Cys) showed no signs of peripheral retinal dystrophy, and did not manifest any disease characteristics typical of the
gene mutation. Consequently, we conclude that the variant did not contribute to the phenotype. According to standards and guidelines for the interpretation of sequence variants,
c.134A>G, p.(Tyr45Cys) revealed likely benign features.
Precise genetic diagnosis in RPE65-mediated retinitis pigmentosa (RP) is necessary to establish eligibility for genetic treatment with voretigene neparvovec: a recombinant adeno-associated viral ...vector providing a functional RPE65 gene. This case report aims to report a novel RP-related point mutation RPE65 c.353G>A, p.(Arg118Lys), a variant of uncertain significance associated with a severe clinical presentation and the striking phenotypic feature of complete macular atrophy. We report the case of a 40-year-old male with inherited retinal dystrophy, all features typical for the RPE65-associated RP, and marked macular atrophy. Genetic testing identified that the patient was a compound heterozygote in trans form with two heterozygous variants: RPE65 c.499G>T, p.(Asp167Tyr) and RPE65 c.353G>A, p.(Arg118Lys). Furthermore, short-wavelength and near-infrared autofluorescence patterns exhibited deficiencies specific to mutations in the visual cycle genes. To the best of our knowledge, RPE65 c.353G>A, p.(Arg118Lys) is the first described point mutation on this locus, among all other reported insertional mutations, currently classified as likely benign and of uncertain significance. We concluded that this variant contributed to the pathological phenotype, demonstrating its significance clearly to be reclassified as likely pathogenic. This being the case, patients with this specific variant in homozygous or compound heterozygous form would be likely candidates for genetic treatment with voretigene neparvovec.
AIM: To invastigate intra- and interobserver reliability of interferometry, tear meniscus height (TMH) measurement and meibography (MBG) of an ocular surface analyzer, LacryDiag (Quantel Medical, ...France). METHODS: Five consecutive measurements and subsequent analysis of interferometry, TMH, and MBG were recorded by two examiners using the LacryDiag. To assess intra- and interobserver reliability, we used Cohen’s kappa for categorical variables (interferometry), or intraclass correlation coefficient for continuous variables (TMH, MBG). RESULTS: Thirty eyes of 30 examinees were included. For both observers, there was excellent intraobserver reliability for MBG (0.955 and 0.970 for observer 1 and 2, respectively). Intraobserver reliability for observer 1 was substantial for interferometry (0.799), and excellent for TMH (0.863). Reliability for observer 2 was moderate for interferometry (0.535) and fair to good for TMH (0.431). Interobserver reliability was poor for interferometry (0.074) and fair to good for TMH (0.680) and MBG (0.414). CONCLUSION: LacryDiag ocular surface analyzer in our study proves to be a reliable noninvasive tool for the evaluation of TMH and MBG. As for interferometry, poor interobserver reliability, fair to good intraobserver reliability for observer 1, and moderate for observer 2, leave room for improvement.
We present two children aged 3 and 5 years who share identical TYR genotype, yet exhibit contrasting phenotypic manifestations in terms of eye, skin, and hair coloration. The patients are ...heterozygous for TYR c.1A>G, p. (Met1?), which is pathogenic, and homozygous for TYR c.1205G>A, p. (Arg402Gln), which is classified as a risk factor. The children manifested diminished visual acuity, nystagmus, and foveal hypoplasia. The first patient presented with hypopigmentation of the skin, hair, and ocular tissues, while the second patient presented with hypopigmentation of the skin, hair, retinal pigment epithelium, and choroid with dark brown irises. Furthermore, the brown-eyed subject presented astigmatic refractive error and both global and local stereopsis capabilities, contrasting with the presentation of hypermetropia, strabismus, and the absence of stereopsis in the blue-eyed individual. Herein, we propose a genotype–phenotype correlation model to elucidate the diverse clinical presentations stemming from biallelic and triallelic pathogenic variants in TYR, establishing a link between the residual tyrosinase activity and resultant phenotypes. According to our proposed model, the severity of TYR variants correlates with distinct albino phenotypes. Our findings propose the potential association between reduced pigmentation levels in ocular tissues and binocular functions, suggesting pigmentation as a possible independent variable influencing the onset of strabismus—an association unreported until now in the existing literature.
The purpose was to define the threshold of normal visual acuity (VA), mean monocular and binocular VA, and interocular difference in the uniform cohort of healthy four-year-old children. All the ...children were recruited from the Croatian National Registry of Early Amblyopia Detection database. LEA Symbols® inline optotypes were used for VA testing at near and distance, binocularly and monocularly. The pass cut-off level was set to ≤0.1 logMAR. The final sample consisted of 58,712 four-year-old children. In total, 83.78% of the children had unremarkable results, and 16.22% of the children were referred to examination. Of those, 92% of the children were referred due to binocular, and 8% of the children due to monocular causes. The children referred due to binocular causes demonstrated a VA of 0.3 ± 0.24, while the children referred due to monocular causes 0.6 ± 0.21. The ROC curve analysis defined the uniform cut-off value for a normative VA of 0.78. We analyzed the largest uniform cohort of 58,712 children, and have determined normative data for binocular and monocular VA tested with gold standard logMAR chart in four-year-old children. The results presented here established no reasoning to further utilize historical protocols in testing VA in preschool children aged ≥ 4 years.
Cilj rada: Razjasniti i ukazati na nejasnoće propisanih postupnika vezanih uz provedbu medicinskih istraživanja s djecom te pozvati na stručnu raspravu s ciljem dolaska do relevantne interpretacije ...propisa. Ispitanici i metode: Pregled literature predmetnih pravilnika, zakona i konvencija u digitalnom i tiskanom izdanju koja se odnose na etički kodeks istraživanja s djecom u medicinskim istraživanjima. Rezultati: Ukupno se nađe četiri pravilnika: Pravilnik za provedbu istraživanja u Kliničkoj bolnici „Sveti Duh“, Pravilnik za provedbu istraživanja Medicinskog fakulteta u Zagrebu te Etički kodeks istraživanja s djecom u medicinskim i nemedicinskim istraživanjima; tri zakona koja se odnose na istraživanja s djecom: Obiteljski zakon Republike Hrvatske, Zakon o zaštiti prava pacijenata te Zakon o provedbi opće uredbe o zaštiti podataka; Konvencija o pravima djeteta pri Ujedinjenim narodima te Hrestomatija hrvatskoga medicinskog prava. Očekivani doprinos području: Pregledom literature nađu se nejasne i nepotpune informacije o sudjelovanju
djece u prospektivnim medicinskim istraživanjima na etički prihvatljiv način. Rad definira nejasnoće vezane uz izradu medicinskih istraživanja s djecom, posebice vremenske odrednice davanja informiranog pristanka za istraživanje od strane djeteta i zakonskog skrbnika, način osiguravanja tajnosti podataka i način osiguravanja pohrane podataka. S obzirom na neujednačene zaključke, iskazana je potreba ujednačavanja odrednica predmetnih zakonskih propisa.
We present a case involving a patient whose clinical phenotype aligns with oculocutaneous albinism (OCA), yet exhibits a complex genotype primarily characterized by variants of unknown significance ...(VUS). An 11-year-old boy manifested iris hypopigmentation and translucency, pronounced photophobia, diminished visual acuity and stereopsis, nystagmus, reduced pigmentation of the retina, and foveal hypoplasia. Genetic testing was performed. A heterozygous missense VUS CAPN5 c.230A>G, p.(Gln77Arg), a heterozygous missense VUS TYR c.1307G>C, p.(Gly436Ala), and a heterozygous missense variant TYR c.1205G>A, p.(Arg402Gln) which was classified as a risk factor, were identified. We hypothesized that the TYR c.1307G>C, p.(Gly436Ala) variant is in genetic disequilibrium with the TYR c.1205G>A, p.(Arg402Gln) variant leading to deficient expression of melanogenic enzymes in retinal cells, resulting in the manifestation of mild OCA. Additionally, this study represents the case where we did not detect chiasmal misrouting in visual evoked potentials, nor did we observe a shift in the distribution of ganglion cell thickness from a temporal to a central position. Moreover, our patient’s case supports the probable benign nature of the CAPN5 c.230A>G, p.(Gln77Arg) variant.
A review of a rare case of a proven mutation in the RP1 gene (RP1c.2029C>T, p. (ARG677*) in a kidney transplant patient was presented herein. According to his medical history, he had tonsillectomy ...performed at the age of 20 due to erythrocyturia, and at the age of 32 he was treated for malignant hypertension. The patient had been diagnosed with chronic renal failure at age 56 years. During an eye examination in 2016, retinitis pigmentosa was suspected and the patient was advised to run further tests. After an ophthalmological examination and tests, genetic testing was performed and a mutation in the RP1 gene encoding a family of proteins which are components of microtubules in photoreceptor primary cilia was proven. The literature search found that mutations in the RP1 gene have so far been exclusively associated with a non-syndromic form of retinal degeneration. However, the RP1 protein is expressed in the kidneys, and it remains unclear why the mutation of this gene so far was only specifically related to retinal photoreceptor function and not to arterial hypertension and renal disease. Primary cilia are thought to act as potential mechanosensory fluid-flow receptors in the vascular endothelium and kidney and their dysfunction results in atherosclerotic changes, hypertension, and chronic renal failure.
The aim of this study was to provide normative databases of Fourier analysis (FA) and Belin-Ambrósio enhanced ectasia display (BAD) in healthy White 4-year-old emmetropic children.
FA parameters ...analyzed were spherical component (SRmin), spherical eccentricity (SEcc), maximal decentration (MD), regular astigmatism at the center (Astigm. C) and periphery (Astigm. P), and irregularity (I). The parameters obtained by BAD included summary indicator BAD D, anterior corneal curvature (K1 and K2, D), maximal keratometry (Kmax, D), maximal Ambrósio relational thinnest (ART max), and pachymetric and BAD indices.
Eighty-nine eyes of eighty-nine 4-year-old children were included. The mean values of FA parameters were the following: SRmin 7.77, SEcc 0.600, MD 0.160, Astigm. C 0.070, Astigm. P 0.050, and I 0.019. The mean K1 and K2 in our study group were 42.92 ± 1.29 D and 43.75 ± 1.41 D, with the mean BAD D value 0.42 ± 0.67. The mean PPI min 0.629 ± 0.117, PPI max 1.059 ± 0.155, PPI avg 0.847 ± 0.103, Kmax 44.10 ± 1.39, and median of ART max 515.0 were recorded. No statistically significant differences between male and female sex in any of FA or BAD parameters were found.
This is the first study providing large normative data on FA and BAD in 4-year-old White emmetropic children. We proposed a cutoff D value for early ectasia and clinical keratoconus in 4-year-old children.
