{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T07:37:56Z","timestamp":1769499476178,"version":"3.49.0"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,10,21]],"date-time":"2014-10-21T00:00:00Z","timestamp":1413849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Mucopolysaccharidosis type I is a rare autosomal recessive disorder caused by deficiency of \u03b1\u2010<jats:sc>l<\/jats:sc>\u2010iduronidase (<jats:styled-content style=\"fixed-case\">IDUA<\/jats:styled-content>) which leads to a wide spectrum of clinical severity. Here, we describe the case of four male patients who present the previously undescribed p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content> mutation. Patient 1 (p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content>\/p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content>) presents, despite multiple joint contractures, an attenuated phenotype. Patient 2 (p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content>\/p.<jats:styled-content style=\"fixed-case\">W402X<\/jats:styled-content>) was diagnosed at 4\u2009years of age with bone dysplasia, coarse facies, limited mobility, claw hands and underwent bilateral carpal tunnel surgery at 6\u2009years of age. Patients 3 and 4 (both p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content>\/p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content>) are brothers. Patient 3 was diagnosed at 4\u2009years of age, when presented claw hands, lower limb and shoulder pain, restricted articular movement and bilateral carpal tunnel syndrome. Patient 4 was diagnosed at 17\u2009months of age when presented lower limb pain at night, respiratory allergy and repeated upper airways infections. Bioinformatics analysis indicates that p.<jats:styled-content style=\"fixed-case\">L18P<\/jats:styled-content> mutation reduces the signal peptide to 25 amino acids and alters its secondary structure. In conclusion, we report a new <jats:italic><jats:styled-content style=\"fixed-case\">IDUA<\/jats:styled-content><\/jats:italic> variant that alters the structure of the signal peptide, which likely impairs transport to lysosomes. Moreover, it leads to a distinct attenuated phenotype with mainly bone and cartilage symptoms, without visceromegalies, heart disease, or cognitive impairment.<\/jats:p>","DOI":"10.1111\/cge.12507","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T13:47:20Z","timestamp":1411652840000},"page":"376-380","source":"Crossref","is-referenced-by-count":7,"title":["p.<scp>L18P<\/scp>: a novel <scp>IDUA<\/scp> mutation that causes a distinct attenuated phenotype in mucopolysaccharidosis type I patients"],"prefix":"10.1111","volume":"88","author":[{"given":"G.","family":"Pasqualim","sequence":"first","affiliation":[{"name":"Post\u2010Graduate Program on Genetics and Molecular Biology UFRGS  Porto Alegre Brazil"},{"name":"Gene Therapy Center, Experimental Research Center Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.G.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.G.G.","family":"da Fonseca","sequence":"additional","affiliation":[{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Szlago","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para el Estudio de las Enfermedades metab\u00f3licas (FESEN)  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Schenone","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para el Estudio de las Enfermedades metab\u00f3licas (FESEN)  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lemes","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica Hospital Italiano  Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.V.M.","family":"Rojas","sequence":"additional","affiliation":[{"name":"Genzyme Genzyme Latin America\u00a0\u2013\u00a0A Sanofi Company  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Matte","sequence":"additional","affiliation":[{"name":"Post\u2010Graduate Program on Genetics and Molecular Biology UFRGS  Porto Alegre Brazil"},{"name":"Gene Therapy Center, Experimental Research Center Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"},{"name":"Department of Genetics UFRGS  Porto Alegre Brazil"},{"name":"INAGEMP  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Giugliani","sequence":"additional","affiliation":[{"name":"Post\u2010Graduate Program on Genetics and Molecular Biology UFRGS  Porto Alegre Brazil"},{"name":"Gene Therapy Center, Experimental Research Center Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"},{"name":"Department of Genetics UFRGS  Porto Alegre Brazil"},{"name":"INAGEMP  Porto Alegre Brazil"},{"name":"Medical Genetics Service Hospital de Clinicas de Porto Alegre  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,10,21]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"3421","volume-title":"The metabolic and molecular basis of inherited disease","author":"Neufeld EF","year":"2001"},{"key":"e_1_2_5_3_1","unstructured":"Human Gene Mutation Database [Internet]. 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