{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:20:37Z","timestamp":1772205637290,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004385","name":"Universiteit Gent","doi-asserted-by":"publisher","award":["BOF 01N04516C"],"award-info":[{"award-number":["BOF 01N04516C"]}],"id":[{"id":"10.13039\/501100004385","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Academy of Dermatovenereology","award":["PPRC-2018-50"],"award-info":[{"award-number":["PPRC-2018-50"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Occipital horn syndrome (OHS) is a rare connective tissue disorder caused by pathogenic variants in ATP7A, encoding a copper transporter. The main clinical features, including cutis laxa, bony exostoses, and bladder diverticula are attributed to a decreased activity of lysyl oxidase (LOX), a cupro-enzyme involved in collagen crosslinking. The absence of large case series and natural history studies precludes efficient diagnosis and management of OHS patients. This study describes the clinical and molecular characteristics of two new patients and 32 patients previously reported in the literature. We report on the need for long-term specialized care and follow-up, in which MR angiography, echocardiography and spirometry should be incorporated into standard follow-up guidelines for OHS patients, next to neurodevelopmental, orthopedic and urological follow-up. Furthermore, we report on ultrastructural abnormalities including increased collagen diameter, mild elastic fiber abnormalities and multiple autophagolysosomes reflecting the role of lysyl oxidase and defective ATP7A trafficking as pathomechanisms of OHS.<\/jats:p>","DOI":"10.3390\/genes10070528","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T11:49:38Z","timestamp":1562932178000},"page":"528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Defining the Clinical, Molecular and Ultrastructural Characteristics in Occipital Horn Syndrome: Two New Cases and Review of the Literature"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0231-6861","authenticated-orcid":false,"given":"Aude","family":"Beyens","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyaran","family":"Van Meensel","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lore","family":"Pottie","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riet","family":"De Rycke","sequence":"additional","affiliation":[{"name":"Department for Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"},{"name":"VIB Center for Inflammation Research, 9000 Ghent, Belgium"},{"name":"Ghent University Expertise Centre for Transmission Electron Microscopy and VIB BioImaging Core, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel","family":"De Bruyne","sequence":"additional","affiliation":[{"name":"Department for Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"},{"name":"VIB Center for Inflammation Research, 9000 Ghent, Belgium"},{"name":"Ghent University Expertise Centre for Transmission Electron Microscopy and VIB BioImaging Core, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Femke","family":"Baeke","sequence":"additional","affiliation":[{"name":"Department for Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"},{"name":"VIB Center for Inflammation Research, 9000 Ghent, Belgium"},{"name":"Ghent University Expertise Centre for Transmission Electron Microscopy and VIB BioImaging Core, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-7647","authenticated-orcid":false,"given":"Piet","family":"Hoebeke","sequence":"additional","affiliation":[{"name":"Department of Urology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Plasschaert","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Loeys","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, University of Antwerp\/Antwerp University Hospital, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie","family":"De Schepper","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie","family":"Symoens","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-4205","authenticated-orcid":false,"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1136\/jmg.34.4.265","article-title":"Menkes disease: Recent advances and new aspects","volume":"344","author":"Tumer","year":"1997","journal-title":"J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/ejhg.2009.187","article-title":"Menkes disease","volume":"185","author":"Tumer","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrneurol.2010.180","article-title":"ATP7A-related copper transport diseases-emerging concepts and future trends","volume":"71","author":"Kaler","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Royce, P.M., and Steinman, B. (2002). Menkes disease and the occipital horn syndrome. Connective Tissue and Its Heritable Disorders, Wiley-Liss.","DOI":"10.1002\/0471221929"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1148\/radiology.152.3.6463246","article-title":"Type IX Ehlers-Danlos syndrome. A new variant with pathognomonic radiographic features","volume":"1523","author":"Sartoris","year":"1984","journal-title":"Radiology"},{"key":"ref_6","first-page":"570","article-title":"Similar splicing mutations of the Menkes\/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse","volume":"563","author":"Das","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1056\/NEJM198007103030201","article-title":"X-linked cutis laxa: Defective cross-link formation in collagen due to decreased lysyl oxidase activity","volume":"3032","author":"Byers","year":"1980","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1093\/hmg\/9.19.2845","article-title":"The Menkes copper transporter is required for the activation of tyrosinase","volume":"919","author":"Petris","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/BF01802032","article-title":"Copper deficiency in the mitochondria of cultured skin fibroblasts from patients with Menkes syndrome","volume":"124","author":"Kodama","year":"1989","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1042\/bj1920579","article-title":"Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes\u2019 syndrome","volume":"1922","author":"Royce","year":"1980","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1086\/321290","article-title":"A novel frameshift mutation in exon 23 of ATP7A (MNK) results in occipital horn syndrome and not in Menkes disease","volume":"692","author":"Dagenais","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s100249900011","article-title":"Metabolic and molecular bases of Menkes disease and occipital horn syndrome","volume":"11","author":"Kaler","year":"1998","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/humu.22266","article-title":"An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome","volume":"343","author":"Tumer","year":"2013","journal-title":"Hum Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ceb.2019.02.009","article-title":"Trafficking mechanisms of P-type ATPase copper transporters","volume":"59","author":"Hartwig","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00418-013-1123-8","article-title":"Golgi in copper homeostasis: A view from the membrane trafficking field","volume":"1403","author":"Polishchuk","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1006\/geno.1995.1175","article-title":"Molecular-Structure of the Menkes Disease Gene (ATP7A)","volume":"28","author":"Dierick","year":"1995","journal-title":"Genomics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0888-7543(95)80160-N","article-title":"Characterization of the exon structure of the Menkes disease gene using vectorette PCR","volume":"263","author":"Tumer","year":"1995","journal-title":"Genomics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/ng0193-14","article-title":"Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein","volume":"31","author":"Chelly","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/ng0193-20","article-title":"Isolation of a Partial Candidate Gene for Menkes Disease by Positional Cloning","volume":"31","author":"Mercer","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/ng0193-7","article-title":"Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase","volume":"31","author":"Vulpe","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41598-017-00618-6","article-title":"Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease","volume":"7","author":"Skjorringe","year":"2017","journal-title":"Sci. Rep.-Uk"},{"key":"ref_22","first-page":"673","article-title":"Molecular pathogenesis of Wilson and Menkes disease: Correlation of mutations with molecular defects and disease phenotypes","volume":"4411","author":"Muller","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature10191","article-title":"Crystal structure of a copper-transporting PIB-type ATPase","volume":"475","author":"Gourdon","year":"2011","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11170","DOI":"10.1074\/jbc.274.16.11170","article-title":"The role of GMXCXXC metal binding sites in the copper-induced redistribution of the Menkes protein","volume":"27416","author":"Strausak","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nsb0198-47","article-title":"Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATpase","volume":"51","author":"Gitschier","year":"1998","journal-title":"Nat. Struct. Biol."},{"key":"ref_26","first-page":"883","article-title":"Diverse mutations in patients with Menkes disease often lead to exon skipping","volume":"555","author":"Das","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/ng1094-195","article-title":"Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus","volume":"82","author":"Kaler","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0002-9297(07)64297-9","article-title":"A C2055T transition in exon 8 of the ATP7A gene is associated with exon skipping in an occipital horn syndrome family","volume":"611","author":"Ronce","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/hmg\/7.3.465","article-title":"Constitutive skipping of alternatively spliced exon 10 in the ATP7A gene abolishes Golgi localization of the menkes protein and produces the occipital horn syndrome","volume":"73","author":"Qi","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jpeds.2004.04.033","article-title":"Variable clinical expression of an identical mutation in the ATP7A gene for Menkes disease\/occipital horn syndrome in three affected males in a single family","volume":"1451","author":"Borm","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1086\/302857","article-title":"Similar splice-site mutations of the ATP7A gene lead to different phenotypes: Classical Menkes disease or occipital horn syndrome","volume":"664","author":"Moller","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/B978-0-12-363708-6.50009-6","article-title":"Lysyl oxidase","volume":"8","author":"Siegel","year":"1979","journal-title":"Int. Rev. Connect. Tissue Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1212\/WNL.40.2.370","article-title":"Dopamine-beta-hydroxylase deficiency in humans","volume":"402","author":"Biaggioni","year":"1990","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1056\/NEJM198606053142307","article-title":"Isolated failure of autonomic noradrenergic neurotransmission. Evidence for impaired beta-hydroxylation of dopamine","volume":"31423","author":"Robertson","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/1096-8628(2001)9999:9999<::AID-AJMG1167>3.0.CO;2-R","article-title":"ATP7A gene mutations in 16 patients with Menkes disease and a patient with occipital horn syndrome","volume":"993","author":"Gu","year":"2001","journal-title":"Am. J. Med. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-510X(93)90081-9","article-title":"Central nervous system involvement and generalized muscular atrophy in occipital horn syndrome: Ehlers-Danlos type IX. A first Japanese case","volume":"1161","author":"Wakai","year":"1993","journal-title":"J. Neurol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/(SICI)1096-8628(19961002)65:1<44::AID-AJMG7>3.0.CO;2-Y","article-title":"Distinctive Menkes disease variant with occipital horns: Delineation of natural history and clinical phenotype","volume":"651","author":"Proud","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1093\/hmg\/5.11.1737","article-title":"A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome","volume":"511","author":"Levinson","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_39","first-page":"179","article-title":"Occipital Horn syndrome in a 2-year-old boy","volume":"83","author":"Loeys","year":"1999","journal-title":"Clin. Dysmorphol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/ejhg.2013.191","article-title":"Occipital horn syndrome and classical Menkes Syndrome caused by deep intronic mutations, leading to the activation of ATP7A pseudo-exon","volume":"224","author":"Yasmeen","year":"2014","journal-title":"Eur. J. Hum. Genet (EJHG)"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/01.gim.0000245578.94312.1e","article-title":"Functional copper transport explains neurologic sparing in occipital horn syndrome","volume":"811","author":"Tang","year":"2006","journal-title":"Genet. Med."},{"key":"ref_42","first-page":"1173","article-title":"13 novel putative mutations in ATP7A found in a cohort of 25 Italian families","volume":"324","author":"Enzo","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1136\/jmg.2007.050013","article-title":"Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease\/occipital horn syndrome","volume":"448","author":"Donsante","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s00256-011-1175-6","article-title":"Occipital horn syndrome in a woman: Skeletal radiological findings","volume":"4011","author":"Bazzocchi","year":"2011","journal-title":"Skeletal Radiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jtemb.2012.04.017","article-title":"Effects of disulfiram treatment in patients with Menkes disease and occipital horn syndrome","volume":"26","author":"Ogawa","year":"2012","journal-title":"J. Trace Elements Med. Biol."},{"key":"ref_46","first-page":"S91","article-title":"Expanding the phenotype of ATP7A-related copper transport diseases: Response to copper treatment","volume":"36","author":"Nascimento","year":"2013","journal-title":"J. Inherit Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.arcped.2015.07.017","article-title":"Multiple bladder diverticula caused by occipital horn syndrome","volume":"2211","author":"Legros","year":"2015","journal-title":"Arch. Pediatr."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Louro, P., Ramos, L., Oliveira, R., Henriques, M., Pereira, E., Kaler, S.G., Pereira, J., Diogo, L., and Garcia, P. (2017, January 5\u20138). Inherited Disorders of Metal Metabolism: A Rare Case of Occipital Horn Syndrome. Proceedings of the 13th International Congress of Inborn Errors of Metabolism, Rio De Janeiro, Brazil.","DOI":"10.1177\/2326409817730396"},{"key":"ref_49","unstructured":"Palcic, I., Cvitkovic Roic, A., Roic, G., Krakar, G., and Jaklin Kekez, A. (2017, January 6\u20137). Bladder diverticula caused by occipital horn syndrome\u2014A case report. Proceedings of the 50th Anniversary meeting of the European Society of Paediatric Nephrology, Glasglow, UK."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Htut, E.P., Offiah, A.C., Holden, S., and Shenker, N.G. (2017). Compelling case of copper conundrum; Occipital horn syndrome. Rheumatology, 56.","DOI":"10.1093\/rheumatology\/kex062.031"},{"key":"ref_51","first-page":"S25","article-title":"Cutis laxa and copper transport anomalies, one gene, two ends of the spectrum","volume":"34","author":"Giacaman","year":"2017","journal-title":"Pediatr. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1136\/jmg.29.6.375","article-title":"Detection and characterisation of an overmodified type III collagen by analysis of non-cutaneous connective tissues in a patient with Ehlers-Danlos syndrome IV","volume":"296","author":"Nuytinck","year":"1992","journal-title":"J. Med. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/hmg\/ddz024","article-title":"Bi-allelic AEBP1 mutations in two patients with Ehlers-Danlos syndrome","volume":"2811","author":"Syx","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1399-0004.1994.tb03986.x","article-title":"Occipital horn syndrome: Report of a patient and review of the literature","volume":"451","author":"Tsukahara","year":"1994","journal-title":"Clin. Genet."},{"key":"ref_55","first-page":"71","article-title":"Skeletal dysplasia, occipital horns, diarrhea and obstructive uropathy\u2014A new hereditary syndrome","volume":"115","author":"Lazoff","year":"1975","journal-title":"Birth Defects Orig. Article Series."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/humu.22165","article-title":"Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa","volume":"341","author":"Callewaert","year":"2013","journal-title":"Hum Mutat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ajmg.a.30299","article-title":"The natural history, including orofacial features of three patients with Ehlers-Danlos syndrome, dermatosparaxis type (EDS type VIIC)","volume":"1311","author":"Malfait","year":"2004","journal-title":"Am. J. Med. Genet. Part A."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1086\/301726","article-title":"Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses","volume":"622","author":"Wuyts","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jurik, A.G., Jorgensen, P.H., and Mortensen, M.M. (2019). Whole-body MRI in assessing malignant transformation in multiple hereditary exostoses and enchondromatosis: Audit results and literature review. Skeletal Radiol., [Epub ahead of print].","DOI":"10.1007\/s00256-019-03268-z"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jtemb.2014.07.022","article-title":"Small amounts of functional ATP7A protein permit mild phenotype","volume":"31","author":"Moller","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-4157(95)00017-8","article-title":"Structural organization, ion transport, and energy transduction of P-type ATPases","volume":"12861","author":"Moller","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1086\/505407","article-title":"Evidence that translation reinitiation leads to a partially functional Menkes protein containing two copper-binding sites","volume":"792","author":"Paulsen","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/exd.12025","article-title":"The complexity of elastic fibre biogenesis in the skin--A perspective to the clinical heterogeneity of cutis laxa","volume":"222","author":"Uitto","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1042\/BJ20101061","article-title":"Identification of binding partners interacting with the alpha1-N-propeptide of type V collagen","volume":"4332","author":"Symoens","year":"2011","journal-title":"Biochem. J."},{"key":"ref_65","first-page":"201","article-title":"Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome. Laboratory investigation","volume":"402","author":"Vogel","year":"1979","journal-title":"J. Techn. Methods Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/humu.20107","article-title":"The molecular basis of classic Ehlers-Danlos syndrome: A comprehensive study of biochemical and molecular findings in 48 unrelated patients","volume":"251","author":"Malfait","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0968-4328(00)00043-3","article-title":"Type V collagen: Heterotypic type I\/V collagen interactions in the regulation of fibril assembly","volume":"323","author":"Birk","year":"2001","journal-title":"Micron (Oxford, England: 1993)"},{"key":"ref_68","first-page":"394","article-title":"Differential ultrastructural aberrations of collagen fibrils in Ehlers-Danlos syndrome types I-IV as a means of diagnostics and classification","volume":"934","author":"Hausser","year":"1994","journal-title":"Hum. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/7\/528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:05:12Z","timestamp":1760187912000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/7\/528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,12]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["genes10070528"],"URL":"https:\/\/doi.org\/10.3390\/genes10070528","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,12]]}}}