{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:35:18Z","timestamp":1782894918386,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hyaluronan and proteoglycan link protein 1 encodes HAPLN1, a critical structural protein in the extracellular matrix (ECM), essential for maintaining tissue architecture and integrity. HAPLN1 mediates stable interactions between hyaluronan and proteoglycans, crucial elements of the ECM that confer structural stability, elasticity, and functional regulation to connective tissues. Aberrations in HAPLN1 expression or function have been implicated in various pathological conditions, including inflammation and tumorigenesis in humans and skeletal dysplasias in mice. To the best of our knowledge,\n                    <jats:italic>HAPLN1<\/jats:italic>\n                    has not been implicated in human skeletal dysplasia. Herein, we report a novel homozygous missense variant in\n                    <jats:italic>HAPLN1<\/jats:italic>\n                    in four individuals from an extended consanguineous Kuwaiti family, co\u2010segregating with a skeletal dysplasia phenotype. Affected individuals presented with shortened long bones of both upper and lower limbs, square\u2010shaped iliac wings, narrowed sciatic notches, flattened acetabular roofs, progressive narrowing of the lumbar interpedicular distance with widened intervertebral disc spaces, and short, stubby metacarpal bones. Our findings identify\n                    <jats:italic>HAPLN1<\/jats:italic>\n                    as a candidate gene underlying a newly described autosomal recessive skeletal dysplasia.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70237","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:44:17Z","timestamp":1782888257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic Variant in\n                    <i>HAPLN1<\/i>\n                    is Associated With Skeletal Dysplasia With or Without Congenital Heart Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2583-4499","authenticated-orcid":false,"given":"Reem M.","family":"Elshafie","sequence":"first","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-0311","authenticated-orcid":false,"given":"Hind","family":"Alsharhan","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"},{"name":"Department of Pediatrics, College of Medicine Kuwait University  Safat Kuwait"},{"name":"Department of Pediatrics Farwaniya Hospital, Ministry of Health  Sabah Al\u2010Nasser Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanai","family":"Abulabqah","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Janicijevic","sequence":"additional","affiliation":[{"name":"Department of Radiology Jahra Hospital, Ministry of Health  Al Jahra Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuwayer H.","family":"Alrashidi","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"Omar","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Bastaki","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3607-395X","authenticated-orcid":false,"given":"Naif A. M.","family":"Almontashiri","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases Taibah University  Almadinah Almunwarah Saudi Arabia"},{"name":"Faculty of Applied Medical Sciences Taibah University  Almadinah Almunwarah Saudi Arabia"},{"name":"Research Department King Khaled Eye Specialist Hospital  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-3423","authenticated-orcid":false,"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center Ministry of Health  Sulaibikhat Kuwait"},{"name":"Department of Pediatrics, College of Medicine Kuwait University  Safat Kuwait"},{"name":"Section of Child Neurology, Department of Pediatrics Adan Hospital, Ministry of Health  Hadiya Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmedt.2025.1565810","article-title":"Biomaterials in Tissue Repair and Regeneration: Key Insights From Extracellular Matrix Biology","volume":"7","author":"Abolhasani S.","year":"2025","journal-title":"Frontiers in Medical Technology"},{"issue":"1","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ymgme.2014.09.001","article-title":"Novel Pathogenic COL11A1\/COL11A2 Variants in Stickler Syndrome Detected by Targeted NGS and Exome Sequencing","volume":"113","author":"Acke F. 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Assembly With Hyaluronate and Link Protein as Studied by Electron Microscopy","volume":"253","author":"Morgelin M.","year":"1988","journal-title":"Biochemical Journal"},{"issue":"3","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0720-048X(01)00397-7","article-title":"The Diagnosis of Skeletal Dysplasias: A Multidisciplinary Approach","volume":"40","author":"Mortier G. R.","year":"2001","journal-title":"European Journal of Radiology"},{"issue":"12","key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/ajmg.a.61366","article-title":"Nosology and Classification of Genetic Skeletal Disorders: 2019 Revision","volume":"179","author":"Mortier G. R.","year":"2019","journal-title":"American Journal of Medical Genetics. 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