{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:11:43Z","timestamp":1779192703193,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T00:00:00Z","timestamp":1473638400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    von Hippel-Lindau (VHL) disease is caused by mutations in the\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    tumor suppressor gene. As tumors that develop in the context of VHL also occur in a sporadic context, the frequency of this syndrome may be underestimated. Our aim was to identify\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    gene mutations in Argentinian patients who fulfilled the clinical criteria for type 1 VHL disease and in patients with VHL-associated manifestations that did not meet these criteria.\n                    <jats:italic toggle=\"yes\">Methods:<\/jats:italic>\n                    We performed a retrospective cohort study, including patients who met current diagnostic criteria for type 1 VHL (Group 1,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200919) and patients with VHL-associated manifestations that did not meet these criteria (Group 2,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200921). Genomic DNA was extracted from peripheral blood leukocytes. Mutation analysis involved DNA sequencing, while large deletions were determined by universal primer quantitative fluorescent multiplex polymerase chain reaction (UPQFM-PCR) and multiplex ligation-dependent probe amplification (MLPA) analysis.\n                    <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    mutations were detected in 16\/19 (84.2%) patients in Group 1 and included: gross deletions (4\/16); nonsense mutations (6\/16); frameshift mutations (4\/16); missense mutations (1\/16); and splicing mutations (1\/16). Three of these mutations were novel. No alterations were found in 3 of 19 VHL patients. In Group 2, one nonsense\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    mutation was detected in a young patient with a solitary central nervous system hemangioblastoma without familial history. A study of 30 first-degree relatives revealed four carriers with\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    mutations.\n                    <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic>\n                    We found three novel mutations in the VHL gene in our population. Our results emphasize the importance of a complete genetic study of\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    to confirm type 1 VHL disease, not only in patients with clinical diagnostic criteria but also in those presenting a single typical manifestation.\n                  <\/jats:p>","DOI":"10.1089\/gtmb.2016.0204","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T16:49:57Z","timestamp":1473698997000},"page":"771-776","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>VHL<\/i>\n                    Germline Mutations in Argentinian Patients with Clinical Diagnoses or Single Typical Manifestations of Type 1 von Hippel-Lindau Disease"],"prefix":"10.1177","volume":"20","author":[{"given":"Cecilia","family":"Math\u00f3","sequence":"first","affiliation":[{"name":"Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Sans\u00f3","sequence":"additional","affiliation":[{"name":"Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanca","family":"Diez","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Lucha contra las Enfermedades Neurol\u00f3gicas de la Infancia","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Barontini","sequence":"additional","affiliation":[{"name":"Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia A.","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,9,12]]},"reference":[{"key":"e_1_3_3_2_1","first-page":"1057","article-title":"454 Next generation-sequencing outperforms allele-specific PCR, sanger sequencing, and pyrosequencing for routine KRAS mutation analysis of formalin-fixed, paraffin-embedded samples","volume":"6","author":"Altimari A","year":"2013","unstructured":"Altimari A, , De Biase D, , De Maglio G, et al. (2013) 454 Next generation-sequencing outperforms allele-specific PCR, sanger sequencing, and pyrosequencing for routine KRAS mutation analysis of formalin-fixed, paraffin-embedded samples. 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(1996) Expression pattern of the von Hippel-Lindau protein in human tissues. Lab Invest, 75:231-238.","journal-title":"Lab Invest"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.4.328"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(64)90107-X"},{"key":"e_1_3_3_23_1","first-page":"1909","article-title":"Hemangioblastomas of the retina: impact of von Hippel-Lindau disease","volume":"41","author":"Niemel\u00e4 M","year":"2000","unstructured":"Niemel\u00e4 M, , Lemeta S, , Sainio M, et al. (2000) Hemangioblastomas of the retina: impact of von Hippel-Lindau disease. 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