Genetic screening of Russian Usher syndrome patients toward selection for gene therapy.

Autor: Ivanova ME; a Oftalmic LLC , Moscow , Russia., Trubilin VN; b Center of Ophthalmology , Federal Medical-Biological Agency State Research Center , Burnasyan, Moscow , Russia., Atarshchikov DS; c Central Clinical Hospital under President Affairs , Moscow , Russia., Demchinsky AM; d Sensor-Tech Scientific and Industrial Laboratory , Moscow , Russia., Strelnikov VV; e Federal State Budgetary Institution , Research Centre for Medical Genetics , Moscow , Russia., Tanas AS; e Federal State Budgetary Institution , Research Centre for Medical Genetics , Moscow , Russia., Orlova OM; b Center of Ophthalmology , Federal Medical-Biological Agency State Research Center , Burnasyan, Moscow , Russia., Machalov AS; f Surdology and Otoneurology Departments , Scientific and Clinical Center for Otorhinolaryngology of FMBA of Russia , Moscow , Russia., Overchenko KV; f Surdology and Otoneurology Departments , Scientific and Clinical Center for Otorhinolaryngology of FMBA of Russia , Moscow , Russia., Markova TV; e Federal State Budgetary Institution , Research Centre for Medical Genetics , Moscow , Russia., Golenkova DM; b Center of Ophthalmology , Federal Medical-Biological Agency State Research Center , Burnasyan, Moscow , Russia., Anoshkin KI; e Federal State Budgetary Institution , Research Centre for Medical Genetics , Moscow , Russia., Volodin IV; e Federal State Budgetary Institution , Research Centre for Medical Genetics , Moscow , Russia., Zaletaev DV; g Laboratory of Medical Genetics, Institute of Molecular Medicine , I. M. Sechenov First Moscow State Medical University , Moscow , Russia., Pulin AA; h Laboratory of Cell Biology and Developmental Pathology , Federal State Budgetary Scientific Institution 'Institute of General Pathology and Pathophysiology' , Moscow , Russia., Nadelyaeva II; i Federal State Budget Institution of Higher Education , A.I. Yevdokimov Moscow State University of Medicine and Dentistry, The Ministry of Health Care of the Russia., Kalinkin AI; e Federal State Budgetary Institution , Research Centre for Medical Genetics , Moscow , Russia.; g Laboratory of Medical Genetics, Institute of Molecular Medicine , I. M. Sechenov First Moscow State Medical University , Moscow , Russia., Barh D; j Center for Genomics and Applied Gene Technology , Institute of Integrative Omics and Applied Biotechnology (IIOAB) , Nonakuri, Purba Medinipur , West Bengal , India.; k Division of Bioinformatics and Computational Genomics , NITTE University Center for Science Education and Research (NUCSER), NITTE (Deemed to be University) , Mangaluru , Karnataka , India.
Jazyk: angličtina
Zdroj: Ophthalmic genetics [Ophthalmic Genet] 2018 Dec; Vol. 39 (6), pp. 706-713. Date of Electronic Publication: 2018 Oct 25.
DOI: 10.1080/13816810.2018.1532527
Abstrakt: Background: Usher syndrome (USH) is heterogeneous in nature and requires genetic test for diagnosis and management. Mutations in USH associated genes are reported in some populations except Russians. Here, we first time represented the mutation spectrum of a Russian USH cohort.
Methods: Twenty-eight patients with USH were selected from 3214 patients from Deaf-Blind Support Foundation "Con-nection" during 2014-2016 following the observational study NCT03319524. Complete ophthalmologic, ENT, and vestibular medical tests were done for clinical characterization. NGS, MLPA, and Sanger sequencing were considered for genetic analysis.
Results: Around 53.57% and 39.28% patients had USH1 and USH2, respectively; 17.85% cases (n = 5/28) had no known mutation. Eleven (73.33%) subjects showed variations in USH1 associated genes MYO7A (72.72%), CDH23 (9.09%), PCDH15 (9.09%), and USH1C (9.09%). Eleven mutations are detected in MYO7A where 54.54% are novel. MYO7A: p.Q18* was most frequent (27.27%) mutation and is associated with early manifestation and most severe clinical picture. Two novel mutations (p.E1301* and c.158-?_318+?del) are detected in PCDH15 gene. Around 90.90% patients suspected to be USH2 are confirmed by genetic testing. Eleven mutations detected in the USH2A gene, where 27.27% were novel. Most common USH2A mutation is p.W3955* (50%) followed by p.E767fs, p.R1653*, and c.8682-9A> G (20% each).
Conclusion: The Russian USH cohort shows both novel and known USH mutations. Clinically the prevalence of USH2 is low (39.28%) and the frequency of MYO7A mutations responsible for USH1B is very high (63.63%, N = 7/11) compared to other cohorts. These seven patients carrying MYO7A mutations are preliminarily eligible for the UshStat® gene therapy.
Databáze: MEDLINE
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