Extended mutation spectrum of Usher syndrome in Finland

Västinsalo, Hanna; Jalkanen, Reetta; Bergmann, Carsten; Neuhaus, Christine; Kleemola, Leenamaija; Jauhola, L.; Bolz, Hanno J.; Sankila, Eeva‐Marja

doi:10.1111/j.1755-3768.2012.02397.x

Cited by 10 publications

(8 citation statements)

References 36 publications

(81 reference statements)

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“…Visual symptoms manifest as retinitis pigmentosa (RP), a progressive retinal dystrophy, with rod and secondary cone photoreceptor dysfunction and ultimate loss. USH is a clinically and genetically heterogeneous disorder, making diagnosis and treatment challenging [ 6 – 9 ]. Previous studies categorized the morphological retinal findings of USH patients, showing that cystoid macula edema and/or cystic macular lesions (CML) are the most common complications in RP associated with USH (USH-RP) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

Sliesoraitytė

Mohand‐Saïd

Sahel

2015

Orphanet J Rare Dis

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BackgroundTo evaluate novel grading system used to quantify optical coherence tomography (OCT) scans for cystic macular lesions (CML) in Usher syndrome (USH) patients, focusing on CML associated alterations in MOY7A and USH2A mutations.MethodsTwo readers evaluated 76 patients’ (mean age 42 ± 14 years) data prospectively uploaded on Eurush database. OCT was used to obtain high quality cross-sectional images through the fovea. The CML was graded as none, mild, moderate or severe, depending on the following features set: subretinal fluid without clearly detectable CML boundaries; central macular thickness; largest diameter of CML; calculated mean of all detectable CML; total number of detectable CML; retinal layers affected by CML. Intra-and inter-grader reproducibility was evaluated.ResultsCML were observed in 37 % of USH eyes, while 45 % were observed in MYO7A and 29 % in USH2A cases. Of those with CML: 52 % had mild, 22 % had moderate and 26 % had severe changes, respectively. CML were found in following retinal layers: 50 % inner nuclear layer, 44 % outer nuclear layer, 6 % retinal ganglion cell layer. For the inter-grader repeatability analysis, agreements rates for CML were 97 % and kappa statistics was 0.91 (95 % CI 0.83-0.99). For the intra-grader analysis, agreement rates for CML were 98 %, while kappa statistics was 0.96 (95 % CI 0.92-0.99).ConclusionsThe novel grading system is a reproducible tool for grading OCT images in USH complicated by CML, and potentially could be used for objective tracking of macular pathology in clinical therapy trials.

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Section: Introductionmentioning

confidence: 99%

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

Sliesoraitytė

Mohand‐Saïd

Sahel

2015

Orphanet J Rare Dis

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“…Other studies have also illustrated this possibility [20,25,[29][30][31][32]. A study based in Italy found that one patient received the USH2A variant from the unaffected father and the MYO7A variant from the unaffected mother, which was heterozygous for mutations in both USH genes [20].…”

Section: Discussionmentioning

confidence: 99%

Multimodal Imaging and Genetic Characteristics of Chinese Patients with USH2A-Associated Nonsyndromic Retinitis Pigmentosa

Chen

Sun

et al. 2020

Preprint

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Background To determine the clinical characteristics and molecular genetic background responsible for USH2A mutations associated with nonsyndromic retinitis pigmentosa (RP) in five Chinese families, a retrospective cross-sectional study was performed. Data of detailed history and comprehensive ophthalmological examinations were extracted from medical charts. Genomic DNA was sequenced by whole-exome sequencing. The pathogenicity predictions were evaluated by in silico analysis. The structural modeling of the wide-type and mutant USH2A proteins was displayed based on I-Tasser software.Results The ultrawide-field fundus imaging showed a distinctive pattern of hyperautofluorescence in the parafoveal ring with macular sparing. Ten USH2A variants were detected, including seven missense mutations, two splicing mutations and one insertion mutation. Six of these variants have already been reported, and the remaining four were novel. Of the de novo mutations, the p.C931Y and p.G4489S mutations were predicted to be deleterious or probably damaging; the p.M4853V mutation was predicted to be neutral or benign; and the IVS22+3A>G mutation was a splicing mutation that could influence mRNA splicing and affect the formation of the hairpin structure of the USH2A protein.Conclusions Our data further confirm that USH2A plays a pivotal role in the maintenance of photoreceptors and expand the spectrum of USH2A mutations that are associated with nonsyndromic RP in Chinese patients.

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“…The gene was found to be connected to the USH3A subtype [ 93 , 94 , 95 , 96 , 97 , 98 ]. A founder mutation, p.Y176X, is present in Finland [ 99 ], but linkages to the USH3 region have also been found in families from the USA and Sweden. Founder mutation among Ashkenazi has been reported as being c.144T > C; p.N48K [ 97 ].…”

Section: Genetics Of Ushmentioning

confidence: 99%

Usher Syndrome

Castiglione

Möller

2022

Audiology Research

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Usher syndrome (USH) is the most common genetic condition responsible for combined loss of hearing and vision. Balance disorders and bilateral vestibular areflexia are also observed in some cases. The syndrome was first described by Albrecht von Graefe in 1858, but later named by Charles Usher, who presented a large number of cases with hearing loss and retinopathy in 1914. USH has been grouped into three main clinical types: 1, 2, and 3, which are caused by mutations in different genes and are further divided into different subtypes. To date, nine causative genes have been identified and confirmed as responsible for the syndrome when mutated: MYO7A, USH1C, CDH23, PCDH15, and USH1G (SANS) for Usher type 1; USH2A, ADGRV1, and WHRN for Usher type 2; CLRN1 for Usher type 3. USH is inherited in an autosomal recessive pattern. Digenic, bi-allelic, and polygenic forms have also been reported, in addition to dominant or nonsyndromic forms of genetic mutations. This narrative review reports the causative forms, diagnosis, prognosis, epidemiology, rehabilitation, research, and new treatments of USH.

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Extended mutation spectrum of Usher syndrome in Finland

Cited by 10 publications

References 36 publications

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

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

Multimodal Imaging and Genetic Characteristics of Chinese Patients with USH2A-Associated Nonsyndromic Retinitis Pigmentosa

Usher Syndrome

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