{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T04:31:36Z","timestamp":1746851496749,"version":"3.37.3"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["20JR5RA334, 21JR1RA039, 21JR11RA119, 22JR5RA652"],"award-info":[{"award-number":["20JR5RA334, 21JR1RA039, 21JR11RA119, 22JR5RA652"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Nos. 82160214\uff0c81960192"],"award-info":[{"award-number":["Nos. 82160214\uff0c81960192"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Cuiying Scientifc and Technological Innovation Program of Lanzhou University Second Hospital","award":["Nos.CY2017-MS18"],"award-info":[{"award-number":["Nos.CY2017-MS18"]}]},{"name":"the Research Fund for Doctoral Tutor of Lanzhou University Second Hospital","award":["No. bdkyjj-02"],"award-info":[{"award-number":["No. bdkyjj-02"]}]},{"name":"the excellent imported talents and doctoral starting fund project of Gansu Provincial Maternal and Child Health Hospital","award":["RCBS-2023-001"],"award-info":[{"award-number":["RCBS-2023-001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Usher syndrome type 3 (USH3) is an autosomal recessive inherited disorder caused by pathogenic variants in the CLRN1 gene.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Object<\/jats:title>\n                <jats:p>To evaluate the genotype-phenotype correlation of Usher syndrome type 3 (USH3) in a deaf-blind Chinese family of 3 generations with 2 patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We collected blood samples and clinical data from all of the pedigree family members. Genomic DNA was isolated from peripheral leukocytes using standard method. Targeted next generation sequencing and Sanger sequencing were performed to find the pathogenic variants in this family. Digital PCR and plasmid overexpression assay were used to verify the pathogenicity of variant sites in different transcripts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>All patients developed bilateral sensorineural hearing loss (SHL), progressive vision loss and nyctalopia. NGS of genes for Usher syndrome, deafness and retinal dystrophy identified a locus mutation in <jats:italic>CLRN1<\/jats:italic> that caused completely different amino acid changes in different transcripts[<jats:italic>CLRN1<\/jats:italic>:c.474T\u2009&gt;\u2009A(P.Cys158Ter) at NM_001256819.2 or c.302T\u2009&gt;\u2009A(p.Val101Asp) at NM_174878.3], and plasmid overexpression experiments confirmed that the c.474T\u2009&gt;\u2009A(P.Cys158Ter, NM_001256819.2) was a pathogenic variant which has never been associated with Usher syndrome in China, and the transcript of this mutation was not the version commonly found worldwide.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The <jats:italic>CLRN1<\/jats:italic>c.474T\u2009&gt;\u2009A(NM_001256819.2) mutation is the causative variant in the Chinese family with USH3. The pathogenicity of different transcripts should be particularly considered in pathogenicity analysis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03348-x","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T02:19:37Z","timestamp":1727230777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A rare transcript homozygous variants in CLRN1(USH3A) causes Usher syndrome type 3 in a Chinese family"],"prefix":"10.1186","volume":"19","author":[{"given":"Suyang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen Yang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieyu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baicheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4736-1607","authenticated-orcid":false,"given":"Yufen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"issue":"6","key":"3348_CR1","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.otc.2015.07.007","volume":"48","author":"T Koffler","year":"2015","unstructured":"Koffler T, Ushakov K, Avraham K. Genetics of hearing loss: Syndromic. Otolaryngol Clin North Am. 2015;48(6):1041\u201361.","journal-title":"Otolaryngol Clin North Am"},{"issue":"2","key":"3348_CR2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1001\/jamaophthalmol.2014.4498","volume":"133","author":"F Blanco-Kelly","year":"2015","unstructured":"Blanco-Kelly F, et al. Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433 patients. JAMA Ophthalmol. 2015;133(2):157\u201364.","journal-title":"JAMA Ophthalmol"},{"issue":"8","key":"3348_CR3","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1097\/GIM.0b013e3181e5afb8","volume":"12","author":"W Kimberling","year":"2010","unstructured":"Kimberling W, et al. Frequency of Usher syndrome in two pediatric populations: implications for genetic screening of deaf and hard of hearing children. Genet Medicine: Official J Am Coll Med Genet. 2010;12(8):512\u20136.","journal-title":"Genet Medicine: Official J Am Coll Med Genet"},{"issue":"1","key":"3348_CR4","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3390\/audiolres12010005","volume":"12","author":"A Castiglione","year":"2022","unstructured":"Castiglione A, M\u00f6ller C. Usher Syndrome Audiol Res. 2022;12(1):42\u201365.","journal-title":"Usher Syndrome Audiol Res"},{"issue":"10","key":"3348_CR5","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1136\/jmg.40.10.767","volume":"40","author":"S Ness","year":"2003","unstructured":"Ness S, et al. Genetic homogeneity and phenotypic variability among Ashkenazi jews with Usher syndrome type III. J Med Genet. 2003;40(10):767\u201372.","journal-title":"J Med Genet"},{"issue":"1","key":"3348_CR6","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1017\/S0022215100096262","volume":"99","author":"S Karjalainen","year":"1985","unstructured":"Karjalainen S, et al. Usher\u2019s syndrome type III: ENG findings in four affected and six unaffected siblings. J Laryngol Otol. 1985;99(1):43\u20138.","journal-title":"J Laryngol Otol"},{"issue":"6","key":"3348_CR7","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1288\/00005537-199506000-00010","volume":"105","author":"L Pakarinen","year":"1995","unstructured":"Pakarinen L, et al. Usher\u2019s syndrome type 3 in Finland. Laryngoscope. 1995;105(6):613\u20137.","journal-title":"Laryngoscope"},{"issue":"6","key":"3348_CR8","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/j.1399-0004.2004.00352.x","volume":"66","author":"E Aller","year":"2004","unstructured":"Aller E, et al. Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability. Clin Genet. 2004;66(6):525\u20139.","journal-title":"Clin Genet"},{"key":"3348_CR9","doi-asserted-by":"crossref","unstructured":"Eeva-Marja Sankila LP, Kaariainen H, Aittomaki K, Karjalainen S. Pertti Sistonen and Albert De La Chapelle, assignment of an Usher syndrome type III (USH3) gene to chromosome 3q. Hum Mol Genet. 4(1): pp. 93\u20138.","DOI":"10.1093\/hmg\/4.1.93"},{"issue":"6","key":"3348_CR10","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/sj.ejhg.5200831","volume":"10","author":"A Adato","year":"2002","unstructured":"Adato A, et al. USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses. Eur J Hum Genet. 2002;10(6):339\u201350.","journal-title":"Eur J Hum Genet"},{"issue":"8","key":"3348_CR11","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.1172\/JCI94351","volume":"128","author":"D Dulon","year":"2018","unstructured":"Dulon D, et al. Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome. J Clin Investig. 2018;128(8):3382\u2013401.","journal-title":"J Clin Investig"},{"issue":"28","key":"3348_CR12","doi-asserted-by":"publisher","first-page":"10188","DOI":"10.1523\/JNEUROSCI.1096-15.2015","volume":"35","author":"SR Gopal","year":"2015","unstructured":"Gopal SR, et al. Zebrafish models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal that Clarin-1 is an essential hair bundle protein. J Neurosci. 2015;35(28):10188\u2013201.","journal-title":"J Neurosci"},{"issue":"1","key":"3348_CR13","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1073\/pnas.70.1.190","volume":"70","author":"G Miller","year":"1973","unstructured":"Miller G, Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci USA. 1973;70(1):190\u20134.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3348_CR14","doi-asserted-by":"publisher","first-page":"100437","DOI":"10.1016\/j.jbc.2021.100437","volume":"296","author":"X Jin","year":"2021","unstructured":"Jin X, et al. An animal model for mitochondrial tyrosyl-tRNA synthetase deficiency reveals links between oxidative phosphorylation and retinal function. J Biol Chem. 2021;296:100437.","journal-title":"J Biol Chem"},{"key":"3348_CR15","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s13023-014-0168-7","volume":"9","author":"M Aparisi","year":"2014","unstructured":"Aparisi M, et al. Targeted next generation sequencing for molecular diagnosis of Usher syndrome. Orphanet J Rare Dis. 2014;9:168.","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"3348_CR16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1136\/bjo.81.1.46","volume":"81","author":"C Hope","year":"1997","unstructured":"Hope C, et al. Usher syndrome in the city of Birmingham\u2013prevalence and clinical classification. Br J Ophthalmol. 1997;81(1):46\u201353.","journal-title":"Br J Ophthalmol"},{"issue":"1","key":"3348_CR17","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1086\/302438","volume":"65","author":"A Adato","year":"1999","unstructured":"Adato A, et al. Possible interaction between USH1B and USH3 gene products as implied by apparent digenic deafness inheritance. Am J Hum Genet. 1999;65(1):261\u20135.","journal-title":"Am J Hum Genet"},{"issue":"6","key":"3348_CR18","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/nchembio.2069","volume":"12","author":"K Alagramam","year":"2016","unstructured":"Alagramam K, et al. A small molecule mitigates hearing loss in a mouse model of Usher syndrome III. Nat Chem Biol. 2016;12(6):444\u201351.","journal-title":"Nat Chem Biol"},{"issue":"4","key":"3348_CR19","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1086\/323610","volume":"69","author":"T Joensuu","year":"2001","unstructured":"Joensuu T, et al. Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am J Hum Genet. 2001;69(4):673\u201384.","journal-title":"Am J Hum Genet"},{"issue":"6","key":"3348_CR20","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/sj.ejhg.5200831","volume":"10","author":"A Adato","year":"2002","unstructured":"Adato A, et al. USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses. Eur J Hum Genetics: EJHG. 2002;10(6):339\u201350.","journal-title":"Eur J Hum Genetics: EJHG"},{"issue":"1","key":"3348_CR21","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1038\/s41598-017-01577-8","volume":"7","author":"AO Khan","year":"2017","unstructured":"Khan AO, et al. A deep intronic CLRN1 (USH3A) founder mutation generates an aberrant exon and underlies severe Usher syndrome on the Arabian Peninsula. Sci Rep. 2017;7(1):1411.","journal-title":"Sci Rep"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03348-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03348-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03348-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T02:20:04Z","timestamp":1727230804000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03348-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3348"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03348-x","relation":{},"ISSN":["1750-1172"],"issn-type":[{"type":"electronic","value":"1750-1172"}],"subject":[],"published":{"date-parts":[[2024,9,20]]},"assertion":[{"value":"19 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Committee of Medical Ethics of Lanzhou University Second Hospital. Written informed consent was obtained from all the participants or the next of kin on the behalf of the minors\/children participants who were involved in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors agree to the publication of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We declare that we have no conflict of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"349"}}