{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:23:57Z","timestamp":1791649437779,"version":"4.3.4"},"reference-count":11,"publisher":"S.C. JURNALUL PENTRU MEDICINA SI VIATA S.R.L","issue":"4","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMedLife"],"abstract":"<jats:p>We present a family in which the first child was diagnosed with dopa-responsive dystonia based on biochemical findings only. Dopa-responsive dystonia is a severe heterogeneous genetic disease. The possibly involved genes are GCH1 and TH.<\/jats:p>\n<jats:p>In their second pregnancy, the parents came for genetic counseling and prenatal diagnosis late, at 12 weeks of gestation. Genetic testing in the affected child was performed, but the results were difficult to interpret. The identified mutations were classified as VOUS \u2013 variants of unknown clinical significance. Although possibly causative, a homozygous variant in the TH gene was not reported before in children with dopa-responsive dystonia. Due to limited time, establishing the fetal prognosis was challenging.<\/jats:p>\n<jats:p>Our report emphasizes the importance of a multidisciplinary approach in the context of new diagnostic techniques, such as Next Generation Sequencing. We illustrate the fact that behind any laboratory result remains sophisticated clinical judgment. We also describe a previously not reported variant of the TH gene in a child with severe, early-onset dystonia.<\/jats:p>","DOI":"10.25122\/jml-2018-0076","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T12:50:18Z","timestamp":1668689418000},"page":"343-345","source":"Crossref","is-referenced-by-count":3,"title":["Prenatal Genetic Testing for Dopa-Responsive Dystonia \u2013 Clinical Judgment in the Context of Next Generation Sequencing"],"prefix":"10.25122","volume":"11","author":[{"given":"Florina","family":"Nedelea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Filantropia Clinical Hospital, Bucharest, Romania","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Veduta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Filantropia Clinical Hospital, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alina Veduta, Filantropia Clinical Hospital, 11 \u2013 13, Ion Mihalache Blvd Postal Code 011171, Bucharest, Romania E-mail: alina.veduta@gmail.com Phone: +40745636052","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Duta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Filantropia Clinical Hospital, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Vayna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Filantropia Clinical Hospital, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Panaitescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Filantropia Clinical Hospital, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gheorghe","family":"Peltecu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Filantropia Clinical Hospital, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Christoph","family":"Duba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Kepler Universit\u00e4tsklinikum Linz, Austria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10755","published-online":{"date-parts":[[2018,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Furukawa Y, Guttman M, Nakamura S, Kish SJ. Dopa-responsive dystonia. In: Frucht SJ, editor. Movement Disorder Emergencies: Diagnosis and Treatment. Springer, New York; 2013. pp 319\u2013340.","DOI":"10.1007\/978-1-60761-835-5_24"},{"key":"ref2","unstructured":"Furukawa Y. Update on dopa-responsive dystonia: locus heterogeneity and biochemical features. Adv Neurol 2004; 94: 127\u201338."},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Thiffault I, Lantos J. The challenge of analyzing the results of Next Generation Sequencing in children. Pediatrics 2016; 137 Suppl 1:S3\u20137.","DOI":"10.1542\/peds.2015-3731C"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL. 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. Genet Med 2015; 17(5):405\u2013424.","DOI":"10.1038\/gim.2015.30"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Leuzzi V, Carducci C, Carducci C, Cardona F, Artiola C, Antonozzi I. Autosomal dominant GTP-CH deficiency presenting as a doparesponsive myoclonus-dystonia syndrome. Neurology 2002; 59(8):1241\u20133.","DOI":"10.1212\/WNL.59.8.1241"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Bandmann O, Nygaard TG, Surtees R, Marsden CD, Wood NW, Harding AE. Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity. Hum Mol Genet 1996; 5(3):403\u20136.","DOI":"10.1093\/hmg\/5.3.403"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Bandmann O, Wood NW. Dopa-responsive dystonia \u2013 the story so far. Neuropediatrics 2002; 33(1):1\u20135.","DOI":"10.1055\/s-2002-23590"},{"key":"ref8","unstructured":"Short Genetic Variations Database (dbSNP). https:\/\/www.ncbi.nlm. nih.gov\/SNP\/snp_ref.cgi?rs=rs41298442"},{"key":"ref9","unstructured":"Exome Sequencing Project (ESP). Exome Variant Server, http:\/\/ evs.gs.washington.edu\/EVS\/ServletManager?variantSNPSummar y=Display+SNP+Summary"},{"key":"ref10","unstructured":"Genome Aggregation Database (gnomAD). Variant: 14:55310817 T \/ C. http:\/\/gnomad.broadinstitute.org\/variant\/14-55310817-T-C"},{"key":"ref11","unstructured":"Online Mendelian Inheritance in Man. OMIM Entry \u2013 # 605407. Segawa Syndrome, autosomal recessive. https:\/\/www.omim.org\/entry\/605407"}],"container-title":["Journal of Medicine and Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/medandlife.org\/wp-content\/uploads\/JMedLife-11-343.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T12:50:29Z","timestamp":1668689429000},"score":1,"resource":{"primary":{"URL":"https:\/\/medandlife.org\/wp-content\/uploads\/JMedLife-11-343.pdf"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["JMedLife-11-343"],"URL":"https:\/\/doi.org\/10.25122\/jml-2018-0076","relation":{},"ISSN":["1844-122X","1844-3117"],"issn-type":[{"value":"1844-122X","type":"print"},{"value":"1844-3117","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10]]}}}