{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:56Z","timestamp":1756166456286,"version":"3.44.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Neuronal ceroid lipofuscinosis (NCL) is one of the most common causes of childhood dementia. NCL type 5 is characterized by epileptic seizures, cognitive decline, and progressive vision loss. Whole exome sequencing was performed, and the identified variant was confirmed by Sanger sequencing. Despite various therapeutic regimens, including novel approaches, seizure control could not be achieved. The disease was caused by a previously undescribed pathogenic variant <jats:italic>CLN5<\/jats:italic>(NM_006493.4):c.368del (p.Arg123LysfsTer4). This is the first known case of NCL type 5 in Russia. Unusually, the patient also had a cervical lymphangioma requiring separate medical and surgical intervention. This case report contributes to our understanding of the natural history of CLN5-associated NCL and may support the development of gene therapy approaches for its treatment.<\/jats:p>","DOI":"10.3389\/fmed.2025.1581597","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:26:42Z","timestamp":1756099602000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal ceroid lipofuscinosis type 5 in Russia: first case report and literature review"],"prefix":"10.3389","volume":"12","author":[{"given":"Olga P.","family":"Parshina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia A.","family":"Buianova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana V.","family":"Mikhaylova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Piliya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alikhan A.","family":"Alikhanov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena K.","family":"Donyush","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zinaida A.","family":"Kondrashova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadezhda V.","family":"Liakhova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg N.","family":"Suchalko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina F.","family":"Samitova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna O.","family":"Shmitko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayya V.","family":"Zazhivikhina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya A.","family":"Votyakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitriy O.","family":"Korostin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"165614","DOI":"10.1016\/j.bbadis.2019.165614","article-title":"The contribution of multicellular model organisms to neuronal ceroid lipofuscinosis research","volume":"1866","author":"Huber","year":"2020","journal-title":"Biochim Biophys Acta Mol basis Dis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"845877","DOI":"10.3389\/fneur.2022.845877","article-title":"Neurophysiological findings in neuronal ceroid lipofuscinoses","volume":"13","author":"Trivisano","year":"2022","journal-title":"Front Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e1228","DOI":"10.1002\/mgg3.1228","article-title":"Neuronal ceroid lipofuscinosis in the Russian population: two novel mutations and the prevalence of heterozygous carriers","volume":"8","author":"Kozina","year":"2020","journal-title":"Mol Genet Genomic Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S1474-4422(18)30368-5","article-title":"Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis","volume":"18","author":"Mole","year":"2019","journal-title":"Lancet Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5729","DOI":"10.3390\/ijms23105729","article-title":"Recent insight into the genetic basis, clinical features, and diagnostic methods for neuronal ceroid Lipofuscinosis","volume":"23","author":"Kamini\u00f3w","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ejpn.2020.12.002","article-title":"Cerliponase alfa changes the natural history of children with neuronal ceroid lipofuscinosis type 2: the first French cohort","volume":"30","author":"Estublier","year":"2021","journal-title":"Eur J Paediatr Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/s41598-021-04526-8","article-title":"System analysis of the sequencing quality of human whole exome samples on BGI NGS platform","volume":"12","author":"Belova","year":"2022","journal-title":"Sci Rep"},{"key":"ref8","year":"2024"},{"key":"ref9","year":"2024"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with burrows-wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref12","year":"2024"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.1093\/bioinformatics\/btr509","article-title":"A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data","volume":"27","author":"Li","year":"2011","journal-title":"Bioinformatics"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/nbt.4235","article-title":"A universal SNP and small-indel variant caller using deep neural networks","volume":"36","author":"Poplin","year":"2018","journal-title":"Nat Biotechnol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1093\/bioinformatics\/btv112","article-title":"Unified representation of genetic variants","volume":"31","author":"Tan","year":"2015","journal-title":"Bioinformatics"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"nwae326","DOI":"10.1093\/nsr\/nwae326","article-title":"Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 7452 exome samples","volume":"11","author":"Barbitoff","year":"202","journal-title":"Natl Sci Rev"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1002\/cphg.93","article-title":"Overview of specifications to the ACMG\/AMP variant interpretation guidelines","volume":"103","author":"Harrison","year":"2019","journal-title":"Curr Protoc Hum Genet"},{"key":"ref21","year":"2024"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"D1333","DOI":"10.1093\/nar\/gkad1005","article-title":"The human phenotype ontology in 2024: phenotypes around the world","volume":"52","author":"Gargano","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1007\/s00405-022-07378-8","article-title":"Efficacy of sirolimus in children with lymphatic malformations of the head and neck","volume":"279","author":"Wiegand","year":"2022","journal-title":"Eur Arch Otorrinolaringol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1111\/j.1528-1157.2000.tb04608.x","article-title":"Epilepsy and antiepileptic drug therapy in juvenile neuronal ceroid lipofuscinosis","volume":"41","author":"Aberg","year":"2000","journal-title":"Epilepsia"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1111\/dmcn.13473","article-title":"Phenotype and natural history of variant late infantile ceroid-lipofuscinosis 5","volume":"59","author":"Simonati","year":"2017","journal-title":"Dev Med Child Neurol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"fcac339","DOI":"10.1093\/braincomms\/fcac339","article-title":"Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis","volume":"5","author":"Murray","year":"2023","journal-title":"Brain Commun"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"536221","DOI":"10.3389\/fgene.2020.536221","article-title":"Functional analysis of a novel CLN5 mutation identified in a patient with neuronal ceroid lipofuscinosis","volume":"11","author":"Luo","year":"2020","journal-title":"Front Genet"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"4735","DOI":"10.1007\/s00018-021-03813-x","article-title":"A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis","volume":"78","author":"Basak","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/humu.10212","article-title":"Human gene mutation database (HGMD): 2003 update","volume":"21","author":"Stenson","year":"2003","journal-title":"Hum Mutat"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/ajmg.10660","article-title":"Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations","volume":"112","author":"Steinfeld","year":"2002","journal-title":"Am J Med Genet"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1212\/WNL.55.4.579","article-title":"Phenotype-genotype correlation in eight patients with Finnish variant late infantile NCL (CLN5)","volume":"55","author":"Holmberg","year":"2000","journal-title":"Neurology"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1581597\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:26:42Z","timestamp":1756099602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1581597\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":31,"alternative-id":["10.3389\/fmed.2025.1581597"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1581597","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,25]]},"article-number":"1581597"}}