Novel grading system for quantification of cystic macular lesions in Usher syndrome

Sliesoraitytė, Ieva; Mohand‐Saïd, Saddek; Sahel, José‐Alain

doi:10.1186/s13023-015-0372-0

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…Serial VEP were normal. The finding of CML revealed by retinal OCT (Figure 1g) may be taken as a hint to progressive retinal dystrophy, as CML have been reported in retinal dystrophies like retinitis pigmentosa (Sliesoraityte, Peto, Mohand-Said, & Sahel, 2015). Furthermore, retrospective analysis of the fundus photographs of this patient revealed progressive narrowing of the arteries, as seen in retinal dystrophies.…”

Section: Subjectsupporting

confidence: 66%

A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome

Koehler

Schuelke

Hell

et al. 2019

American J of Med Genetics Pt A

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Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19‐year‐old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole‐genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21*) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene.

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Section: Subjectsupporting

confidence: 66%

A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome

Koehler

Schuelke

Hell

et al. 2019

American J of Med Genetics Pt A

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“…CML incidence in the arRP group was 20.8% (5/24) in males versus 13.6% (3/22) in females ( p = 0.59), while in the Ush2 group it was 27.8% (5/18) in males versus 32.1% (9/28) in females ( p = 0.82). We classified CML according to the grading system proposed by [16]: in the arRP group 12.5% (1/8) of patients had mild CML, 50% (4/8) moderate, and 37.5% (3/8) severe. In the Ush2 group, 42.9% (6/14) of patients had mild CML, 50% (7/14) moderate, and 7.1% (1/14) severe.…”

Section: Resultsmentioning

confidence: 99%

“…As described above, we classified CML in both groups according to the grading system proposed by Sliesoraityte et al [16]. Similarly to ERM, incidence of CML was higher in Ush2 rather than in arRP patients (30.4% vs. 17.4%, p = 0.2234); moreover, patients with arRP usually have a moderate or severe grade of CML (50 and 37.5%, respectively, p = 0.3181), while Ush2 patients usually have a mild or moderate grade of CML (42.9 and 50%, respectively, p = 0.6357).…”

Section: Discussion/conclusionmentioning

confidence: 99%

Spectral-Domain Optical Coherence Tomography Analysis in Syndromic and Nonsyndromic Forms of Retinitis Pigmentosa due to <b><i>USH2A</i></b> Genetic Variants

et al. 2021

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Introduction: This study aimed to analyze macular structure by using spectral-domain optical coherence tomography (SD-OCT) in a cohort of patients affected by autosomal recessive retinitis pigmentosa and Usher syndrome, due to genetic variants in USH2A gene, and to correlate optical coherence tomography (OCT) parameters with functional and genetic data. Methods: The subjects of this study were 92 patients, 46 syndromic (Usher syndrome type IIa [Ush2]) and 46 nonsyndromic (autosomal recessive RP [arRP]), with clinical and genetic diagnosis of USH2A-related retinal dystrophy, who underwent a complete ophthalmic examination and spectral-domain OCT analysis. The study focused on evaluating the differences between the 2 groups in the following parameters: best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, presence of epiretinal membrane (ERM), and cystic macular lesions (CMLs). Variants in USH2A gene were divided into 3 categories, according to the expected impact (low/high) at protein level of the different variants on each allele. Results: BCVA and EZ width were significantly lower in Ush2 than in arRP patients (p < 0.0001 and p = 0.001). ERM was detected in 34.8% (16/46) of arRP patients and in 65.2% (30/46) of Ush2 patients (p = 0.003). CML was detected in 17.4% (8/46) of arRP patients and 30.4% (14/46) of Ush2 patients (p = 0.14). The allelic distribution was statistically different (p = 0.0003) by dividing the 2 diseases: for Ush2 patients it was 45.7% (high/high), 39.1% (low/high) and 15.2% (low/low); for arRP patients it was 8.7% (high/high), 56.5% (low/high), and 34.8% (low/low). The severity class of the variants significantly affected visual acuity and EZ width parameters (p = 0.004 and p = 0.002, respectively). Conclusion: Retinal disease, as evaluated by means of SD-OCT, shows more advanced degeneration signs in the syndromic than the nonsyndromic form of retinal dystrophy related to USH2A gene. Variant types and allelic profiles are determining factors for the onset of syndromic features. However, since the 3 allelic profiles can be found in both Usher and RP patients, other factors must necessarily play a determining role.

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“…Ocular imaging included color fundus photography (CFP), spectral domain optical coherence tomography (OCT) (6 mm scans centered from the fovea, using a Spectralis imaging platform, Heidelberg, Germany), and fundus autofluorescence (FAF) imaging (HRA, Heidelberg, Germany). Patients with apparent USH were classified with mild, moderate or severe cystoid macular edema (CME), using the grading system of Sliesoraityte et al (2015). The following features were considered: subretinal fluid without clearly detectable cystic macular lesion (CML) boundaries, central macular thickness, largest diameter of CML, calculated mean of all detectable CMLs, total number of detectable CML, and retinal layers affected by CML.…”

Section: Patientsmentioning

confidence: 99%

“…2). Using a grading system for CME (Sliesoraityte et al 2015), moderate and severe cystic lesions were most prevalent among patients with USH1B and biallelic MYO7A variants (Supplementary Table 1). Bilateral pantonal profound sensorineural HI without vestibular dysfunction was the most common form of HI in the USH cohort (Supplementary Table 1).…”

Section: Usher Syndrome As the Most Common Cause Of Dual Sensory Lossmentioning

confidence: 99%

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment

et al. 2021

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Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf–blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf–blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.

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Novel grading system for quantification of cystic macular lesions in Usher syndrome

Cited by 12 publications

References 40 publications

A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome

A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome

Spectral-Domain Optical Coherence Tomography Analysis in Syndromic and Nonsyndromic Forms of Retinitis Pigmentosa due to <b><i>USH2A</i></b> Genetic Variants

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment

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