{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:52:53Z","timestamp":1790484773882,"version":"4.1.0"},"reference-count":45,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Mucolipidoses II and III alpha\/beta (ML II and ML III) are lysosomal disorders in which the essential mannose 6-phosphate recognition marker is not synthesised on to lysosomal hydrolases and other glycoproteins. The disorders are caused by mutations in <jats:italic>GNPTAB<\/jats:italic>, which encodes two of three subunits of the heterohexameric enzyme, <jats:italic>N<\/jats:italic>-acetylglucosamine-1-phosphotransferase.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Clinical, biochemical and molecular findings in 61 probands (63 patients) are presented to provide a broad perspective of these mucolipidoses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                     <jats:italic>GNPTAB<\/jats:italic> was sequenced in all probands and\/or parents. The activity of several lysosomal enzymes was measured in plasma, and GlcNAc-1-phosphotransferase was assayed in leucocytes. Thirty-six patients were studied in detail, allowing extensive clinical data to be abstracted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ML II correlates with near-total absence of phosphotransferase activity resulting from homozygosity or compound heterozygosity for frameshift or nonsense mutations. Craniofacial and orthopaedic manifestations are evident at birth, skeletal findings become more obvious within the first year, and growth is severely impaired. Speech, ambulation and cognitive function are impaired. ML III retains a low level of phosphotransferase activity because of at least one missense or splice site mutation. The phenotype is milder, with minimal delays in milestones, the appearance of facial coarsening by early school age, and slowing of growth after the age of 4 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Fifty-one pathogenic changes in <jats:italic>GNPTAB<\/jats:italic> are presented, including 42 novel mutations. Ample clinical information improves criteria for delineation of ML II and ML III. Phenotype\u2013genotype correlations suggested in more general terms in earlier reports on smaller groups of patients are specified and extended.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.067736","type":"journal-article","created":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T20:19:37Z","timestamp":1247861977000},"page":"38-48","source":"Crossref","is-referenced-by-count":140,"title":["Phenotype and genotype in mucolipidoses II and III alpha\/beta: a study of 61 probands"],"prefix":"10.1136","volume":"47","author":[{"given":"S S","family":"Cathey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J G","family":"Leroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Eaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R J","family":"Simensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R E","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Friez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2009,7,16]]},"reference":[{"key":"2025100521544097000_47.1.38.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.157.3790.804"},{"issue":"4","key":"2025100521544097000_47.1.38.2","first-page":"174","article-title":"I-cell disease","volume":"V","author":"Leroy","year":"1969","journal-title":"Birth Defects Orig Art Ser"},{"key":"2025100521544097000_47.1.38.3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/ajmg.a.32193","article-title":"Molecular order in mucolipidosis II and III nomenclature","volume":"146","author":"Cathey","year":"2008","journal-title":"Am J Med Genet A"},{"key":"2025100521544097000_47.1.38.4","first-page":"2889","article-title":"La pseudopolydystrophie de Hurler","volume":"74","author":"Maroteaux","year":"1966","journal-title":"Presse M\u00e9d"},{"key":"2025100521544097000_47.1.38.5","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1399-0004.1973.tb01165.x","article-title":"Mucolipidosis 3 (pseudo-Hurler polydystrophy): cytological and ultrastructural observations in cultured fibroblast cells","volume":"4","author":"Taylor","year":"1973","journal-title":"Clin Genet"},{"key":"2025100521544097000_47.1.38.6","doi-asserted-by":"crossref","unstructured":"Raas-Rothschild A Zeigler M Cormier-Daire V Bao M Genin E Salomon R Brewer K Mandal H Toth S Roe B Munnich A Canfield WM . 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