{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:26:53Z","timestamp":1773235613575,"version":"3.50.1"},"reference-count":36,"publisher":"Endocrinology Research Centre","issue":"1","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND:<\/jats:bold>\n                    \u00a0Cockayne syndrome is an ultra-rare (1:2.5 million) hereditary disease from the group of progeroid syndromes caused by pathogenic and probable-pathogenic variants in DNA repair genes (\n                    <jats:italic>ERCC8, ERCC6, XPB<\/jats:italic>\n                    \u00a0(\n                    <jats:italic>ERCC3<\/jats:italic>\n                    ),\u00a0\n                    <jats:italic>XPD<\/jats:italic>\n                    \u00a0(\n                    <jats:italic>ERCC2<\/jats:italic>\n                    ) and\u00a0\n                    <jats:italic>XPG<\/jats:italic>\n                    \u00a0(\n                    <jats:italic>ERCC5<\/jats:italic>\n                    )) and characterized by abnormal photosensitivity, congenital cataract, microcephaly, sensorineural hearing loss, nervous system pathology and other multisystem changes. In this manuscript, for the first time in the Russian Federation, we present the results of a clinical and genetic study and follow-up of a Russian cohort of patients.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>MATERIALS AND METHODS:<\/jats:bold>\n                    \u00a0During 2 years, from 2023 to 2025, 7 patients with Cockayne syndrome (4 girls and 3 boys) aged from 3 years 11 months to 16 years 3 months were under clinical observation, of whom 3 patients were diagnosed with Cockayne syndrome type A (causative variants in\u00a0\n                    <jats:italic>ERCC8<\/jats:italic>\n                    \u00a0gene) and 4 patients with type B (causative variants in\u00a0\n                    <jats:italic>ERCC6\u00a0<\/jats:italic>\n                    gene). All patients underwent a comprehensive multidisciplinary examination with evaluation of the results of laboratory and instrumental methods of investigation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS:<\/jats:bold>\n                    \u00a0Based on observational data, we confirmed the incomplete correlation between genotype and phenotype previously described in the literature. With the genotype of Cockayne syndrome type B, previously correlated with severe course of the disease, only one patient had a severe course of the syndrome, two patients had a moderate course, and one patient had a mild course, indicating the variability of the clinical picture within a single gene lesion, and the severity of the course correlated rather with the age of the disease debut: early onset (before 1 year of age) was associated with faster disease progression. Also, regardless of the genotype and severity of the disease course, major diagnostic criteria were identified in all patients: congenital cataract was diagnosed in 5 of 7 observed patients, sensorineural hearing loss in two patients of moderate and mild course of the disease, progressive pathology of the nervous system in 6 of 7 patients, and microcephaly was diagnosed in all patients.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION:\u00a0<\/jats:bold>\n                    This study expands our understanding of the natural course of Cockayne syndrome and our knowledge of the variability of clinical manifestations and severity of the disease course within a single gene lesion. Timely diagnosis and personalized approach of a multidisciplinary team of specialists can slow the progression of complications and improve the quality of life of patients. The work is of value for physicians of various specialties involved in the diagnosis and treatment of orphan genetic diseases, as well as researchers studying the mechanisms of DNA repair and premature aging.\n                  <\/jats:p>","DOI":"10.14341\/probl13634","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T17:22:48Z","timestamp":1773163368000},"page":"115-127","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":0,"title":["Cockayne syndrome: peculiarities of clinical manifestations and algorithm of observation in childhood"],"prefix":"10.14341","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-3093","authenticated-orcid":true,"given":"A. L.","family":"Kungurtseva","sequence":"first","affiliation":[{"name":"Sechenov First Moscow State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-8795","authenticated-orcid":true,"given":"A. V.","family":"Popovich","sequence":"additional","affiliation":[{"name":"Sechenov First Moscow State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-6873","authenticated-orcid":true,"given":"Yu. V.","family":"Tikhonovich","sequence":"additional","affiliation":[{"name":"Sechenov First Moscow State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-7673","authenticated-orcid":true,"given":"T. E.","family":"Ivannikova","sequence":"additional","affiliation":[{"name":"Sechenov First Moscow State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-8574","authenticated-orcid":true,"given":"V. A.","family":"Kovalskaia","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. A.","family":"Vasiliev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5689-0194","authenticated-orcid":true,"given":"A. V.","family":"Vitebskaya","sequence":"additional","affiliation":[{"name":"Sechenov First Moscow State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Karikkineth AC, Scheibye-Knudsen M, Fivenson E, et al. Cockayne syndrome: Clinical features, model systems and pathways. Ageing Res Rev. 2017;33:3-17. doi: https:\/\/doi.org\/10.1016\/j.arr.2016.08.002","DOI":"10.1016\/j.arr.2016.08.002"},{"key":"ref2","unstructured":"Hafsi W, Saleh HM. Cockayne Syndrome. 2024 Jan 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Cockayne EA. Dwarfism with retinal atrophy and deafness. Arch Dis Child. 1936;11(61):1-8. doi: https:\/\/doi.org\/10.1136\/adc.11.61.1","DOI":"10.1136\/adc.11.61.1"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. Mech Ageing Dev. 2013;134(5-6):161-70. doi: https:\/\/doi.org\/10.1016\/j.mad.2013.02.006","DOI":"10.1016\/j.mad.2013.02.006"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Coles WH. Ocular manifestations of Cockayne's syndrome. Am J Ophthalmol. 1969;67(5):762-4. doi: https:\/\/doi.org\/10.1016\/s0002-9394(69)91006-x","DOI":"10.1016\/S0002-9394(69)91006-X"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Calmels N, Botta E, Jia N, Fawcett H, Nardo T, et al. Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome. J Med Genet. 2018;55(5):329-343. doi: https:\/\/doi.org\/10.1136\/jmedgenet-2017-104877","DOI":"10.1136\/jmedgenet-2017-104877"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Le Van Quyen P, Calmels N, Bonni\u00e8re M, Chartier S, Razavi F, et al. Prenatal diagnosis of cerebro-oculo-facio-skeletal syndrome: Report of three fetuses and review of the literature. Am J Med Genet A. 2020;182(5):1236-1242. doi: https:\/\/doi.org\/10.1002\/ajmg.a.61520","DOI":"10.1002\/ajmg.a.61520"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Van Gool AJ, Citterio E, Rademakers S, et al. The Cockayne syndrome B protein, involved in transcription-coupled DNA repair, resides in an RNA polymerase II-containing complex. EMBO J. 1997;16(19):5955-65. doi: https:\/\/doi.org\/10.1093\/emboj\/16.19.5955","DOI":"10.1093\/emboj\/16.19.5955"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Fousteri M, Mullenders LH. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res. 2008;18(1):73-84. doi: https:\/\/doi.org\/10.1038\/cr.2008.6","DOI":"10.1038\/cr.2008.6"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Venema J, Mullenders LH, Natarajan AT, et al. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. Proc Natl Acad Sci U S A. 1990;87(12):4707-11. doi: https:\/\/doi.org\/10.1073\/pnas.87.12.4707","DOI":"10.1073\/pnas.87.12.4707"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Henning KA, Li L, Iyer N, et al. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell. 1995;82(4):555-64. doi: https:\/\/doi.org\/10.1016\/0092-8674(95)90028-4","DOI":"10.1016\/0092-8674(95)90028-4"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Mayne LV, Lehmann AR. Failure of RNA synthesis to recover after UV irradiation: an early defect in cells from individuals with Cockayne's syndrome and xeroderma pigmentosum. Cancer Res. 1982;42(4):1473-8","DOI":"10.1016\/0027-5107(82)90047-1"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Van Hoffen A, Natarajan AT, Mayne LV, et al. Deficient repair of the transcribed strand of active genes in Cockayne's syndrome cells. Nucleic Acids Res. 1993;21(25):5890-5. doi: https:\/\/doi.org\/10.1093\/nar\/21.25.5890","DOI":"10.1093\/nar\/21.25.5890"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Caputo M, Frontini M, Velez-Cruz R, at al. The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth. DNA Repair (Amst). 2013;12(4):293-9. doi: https:\/\/doi.org\/10.1016\/j.dnarep.2013.01.008","DOI":"10.1016\/j.dnarep.2013.01.008"},{"key":"ref15","unstructured":"Moriwaki S. [Cockayne Syndrome]. Brain Nerve. 2019;71(4):390-393. Japanese. doi: https:\/\/doi.org\/10.11477\/mf.1416201282"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Scott RJ, Itin P, Kleijer WJ, et al. Xeroderma pigmentosumCockayne syndrome complex in two patients: absence of skin tumors despite severe deficiency of DNA excision repair. J Am Acad Dermatol. 1993;29(5 Pt 2):883-9. doi: https:\/\/doi.org\/10.1016\/0190-9622(93)70263-s","DOI":"10.1016\/0190-9622(93)70263-S"},{"key":"ref17","unstructured":"Vermeulen W, Scott RJ, Rodgers S, et al. Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3. Am J Hum Genet. 1994;54(2):191-200"},{"key":"ref18","unstructured":"Lafforet D, Dupuy JM. Photosensibilit\u00e9 et r\u00e9paration de l'ADN. Possibilit\u00e9 d'une parent\u00e9 nosologique entre X\u00e9roderma pigmentosum et syndrome de Cockayne [Photosensitization and DNA repair. Possible nosologic relationship between Xeroderma pigmentosum and Cockayne's syndrome]. Arch Fr Pediatr. 1978;35(10 Suppl):65-74"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Vermeulen W, Stefanini M, Giliani S, et al. Xeroderma pigmentosum complementation group H falls into complementation group D. Mutat Res. 1991;255(2):201-8. doi: https:\/\/doi.org\/10.1016\/0921-8777(91)90054-s","DOI":"10.1016\/0921-8777(91)90054-S"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Snyder SH. Retraction for Nouspikel et al. A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: Implications for a second XPG function. Proc Natl Acad Sci U S A. 2006;103(51):19606. doi: https:\/\/doi.org\/10.1073\/pnas.0609759103","DOI":"10.1073\/pnas.0609759103"},{"key":"ref21","unstructured":"Vermeulen W, Jaeken J, Jaspers NG, et al. Xeroderma pigmentosum complementation group G associated with Cockayne syndrome. Am J Hum Genet. 1993;53(1):185-92"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Wilson BT, Stark Z, Sutton RE, et al. The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genet Med. 2016;18(5):483-93. doi: https:\/\/doi.org\/10.1038\/gim.2015.110","DOI":"10.1038\/gim.2015.110"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. 1992;42(1):68-84. doi: https:\/\/doi.org\/10.1002\/ajmg.1320420115","DOI":"10.1002\/ajmg.1320420115"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Rapin I, Lindenbaum Y, Dickson DW, et al. Cockayne syndrome and xeroderma pigmentosum. Neurology. 2000;55(10):1442-9. doi: https:\/\/doi.org\/10.1212\/wnl.55.10.1442","DOI":"10.1212\/WNL.55.10.1442"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Weidenheim KM, Dickson DW, Rapin I. Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration. Mech Ageing Dev. 2009;130(9):619-36. doi: https:\/\/doi.org\/10.1016\/j.mad.2009.07.006","DOI":"10.1016\/j.mad.2009.07.006"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Crome L, Kanjilal GC. Cockayne's syndrome: case report. J Neurol Neurosurg Psychiatry. 1971;34(2):171-8. doi: https:\/\/doi.org\/10.1136\/jnnp.34.2.171","DOI":"10.1136\/jnnp.34.2.171"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Hayashi M, Miwa-Saito N, Tanuma N, et al. Brain vascular changes in Cockayne syndrome. Neuropathology. 2012;32(2):113-7. doi: https:\/\/doi.org\/10.1111\/j.1440-1789.2011.01241.x","DOI":"10.1111\/j.1440-1789.2011.01241.x"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Blin-Rochemaure N, Allani-Essid N, Carlier R, Laugel V, Quijano-Roy S. Place de la neuropathie dans le diagnostic pr\u00e9coce du syndrome de Cockayne: \u00e0 propos de deux cas dans une fratrie [The place of neuropathy in the early diagnosis of Cockayne syndrome: Report on two siblings]. Arch Pediatr. 2017;24(4):353-359. French. doi: https:\/\/doi.org\/10.1016\/j.arcped.2016.12.015","DOI":"10.1016\/j.arcped.2016.12.015"},{"key":"ref29","unstructured":"Laugel V. Cockayne Syndrome. 2000 Dec 28 [updated 2024 Aug 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132025"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. 1992;42(1):68-84. doi: https:\/\/doi.org\/10.1002\/ajmg.1320420115","DOI":"10.1002\/ajmg.1320420115"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Abdel Ghaffar TY, Elsobky ES, Elsayed SM. Cholestasis in patients with Cockayne syndrome and suggested modified criteria for clinical diagnosis. Orphanet J Rare Dis. 2011;6:13. doi: https:\/\/doi.org\/10.1186\/1750-1172-6-13","DOI":"10.1186\/1750-1172-6-13"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Wilson BT, Strong A, O'Kelly S, et al. Metronidazole Toxicity in Cockayne Syndrome: A Case Series. Pediatrics. 2015;136(3):e706-8. doi: https:\/\/doi.org\/10.1542\/peds.2015-0531","DOI":"10.1542\/peds.2015-0531"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Ataee P, Karimi A, Eftekhari K. Hepatic Failure following Metronidazole in Children with Cockayne Syndrome. Case Rep Pediatr. 2020;2020:9634196. doi: https:\/\/doi.org\/10.1155\/2020\/9634196","DOI":"10.1155\/2020\/9634196"},{"key":"ref34","unstructured":"Ben Chehida A, Ghali N, Ben Abdelaziz R, et al. Renal Involvement in 2 Siblings With Cockayne Syndrome. Iran J Kidney Dis. 2017;11(3):253-255"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Stern-Delfils A, Spitz MA, Durand M, et al. Renal disease in Cockayne syndrome. Eur J Med Genet. 2020;63(1):103612. doi: https:\/\/doi.org\/10.1016\/j.ejmg.2019.01.002","DOI":"10.1016\/j.ejmg.2019.01.002"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Wang S, Min Z, Ji Q, et al. Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR\/Cas9- mediated gene correction. Protein Cell. 2020;11(1):1-22. doi: https:\/\/doi.org\/10.1007\/s13238-019-0623-2","DOI":"10.1007\/s13238-019-0623-2"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/13634\/10971","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T17:23:06Z","timestamp":1773163386000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/13634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,7]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3,7]]}},"URL":"https:\/\/doi.org\/10.14341\/probl13634","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"value":"2308-1430","type":"electronic"},{"value":"0375-9660","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3,7]]}}}