{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:31:05Z","timestamp":1773660665221,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tyrosinemia type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, also known as Richner\u2010Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To update disease\u2010causing mutations and current clinical knowledge of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Genetic and clinical information were obtained from a collection of both unreported and previously reported cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report 106 families, represented by 143 individuals, carrying a total of 36 genetic variants, 11 of them not previously known to be associated with the disease. Variants include 3 large deletions, 21 non\u2010synonymous and 5 nonsense amino\u2010acid changes, 5 frameshifts and 2 splice variants. We also report 5 patients from Gran Canaria, representing the largest known group of unrelated families sharing the same <jats:styled-content style=\"fixed-case\">P406L<\/jats:styled-content> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Data analysis did not reveal a genotype\u2010phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cge.13003","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T06:56:43Z","timestamp":1488524203000},"page":"306-317","source":"Crossref","is-referenced-by-count":30,"title":["Tyrosinemia type <scp>II<\/scp>: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation"],"prefix":"10.1111","volume":"92","author":[{"given":"L.","family":"Pe\u00f1a\u2010Quintana","sequence":"first","affiliation":[{"name":"Department of Pediatrics Complejo Hospitalario Universitario Insular\u2010Materno Infantil  Las Palmas de Gran Canaria Spain"},{"name":"CIBER OBN Universidad de Las Palmas de Gran Canaria  Las Palmas de Gran Canaria 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