{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:29:50Z","timestamp":1790908190247,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":["Clinical Case Reports"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The cartilage hair hypoplasia\u2010anauxetic dysplasia (CHH\u2010AD) spectrum represents a group of rare autosomal recessive skeletal dysplasias with significant phenotypic heterogeneity. These disorders are classified based on pathogenic variants in the\n                    <jats:italic>RMRP<\/jats:italic>\n                    ,\n                    <jats:italic>POP1<\/jats:italic>\n                    , and\n                    <jats:italic>NEPRO<\/jats:italic>\n                    genes. Among these, anauxetic dysplasia type 3 (ANXD3), associated with\n                    <jats:italic>NEPRO<\/jats:italic>\n                    variants, manifests as severe skeletal dysplasia characterized by short stature, brachydactyly, skin laxity, and joint hypermobility, with distinct radiographic findings such as ovoid vertebrae, hypoplastic ilia, narrow acetabular angles, and irregular metaphyses. Unlike other CHH\u2010AD subtypes, ANXD3 lacks immunological or gastrointestinal involvement. This study reports three new ANXD3 cases from a consanguineous Iranian family, carrying the homozygous pathogenic variant Chr3:113014014G&gt;A; exon3; c.280C&gt;T; p.Arg94Cys in the\n                    <jats:italic>NEPRO<\/jats:italic>\n                    gene. The clinical phenotypes expand the known spectrum of ANXD3, including unique features such as microcephaly, clubfoot, cataracts, urolithiasis, and hearing impairments, whi12\u201018ch suggest systemic involvement beyond skeletal abnormalities. Diagnostic whole\u2010exome sequencing, supported by Sanger validation, confirmed the autosomal recessive inheritance pattern. A comparative analysis with previously reported ANXD3 cases revealed shared characteristics, including short stature, brachydactyly, and thoracolumbar kyphoscoliosis, while highlighting variability in head size, scalp hair, and systemic features. Microcephaly was observed in our patients, same as previously reported cases, underscoring the phenotypic variability of ANXD3. This study also emphasizes the importance of genetic counseling and early interventions for associated complications, such as orthopedic, renal, and ophthalmological management.\n                  <\/jats:p>","DOI":"10.1002\/ccr3.72355","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:09:16Z","timestamp":1776053356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expanding the Phenotypic Spectrum of Anauxetic Dysplasia Type 3: Reporting an Iranian Family With Unique Systemic Features and\n                    <scp>\n                      <i>NEPRO<\/i>\n                    <\/scp>\n                    Gene Variant"],"prefix":"10.1002","volume":"14","author":[{"given":"Mahnaz Mohammadi","family":"Kian","sequence":"first","affiliation":[{"name":"Momgene Personalized Medicine Center  Tehran Iran"},{"name":"Department of Medical Genetics, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-4251","authenticated-orcid":false,"given":"Sara","family":"Sheikholeslami","sequence":"additional","affiliation":[{"name":"Momgene Personalized Medicine Center  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam Kiani","family":"Feizabadi","sequence":"additional","affiliation":[{"name":"Momgene Personalized Medicine Center  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Mohammad","family":"Roshanaeizadeh","sequence":"additional","affiliation":[{"name":"Momgene Personalized Medicine Center  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atousa","family":"Haghi","sequence":"additional","affiliation":[{"name":"Research Institute for Oncology, Hematology and Cell Therapy Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Reza Salehi","family":"Chaleshtori","sequence":"additional","affiliation":[{"name":"Momgene Personalized Medicine Center  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Reza","family":"Moazzeni","sequence":"additional","affiliation":[{"name":"Momgene Personalized Medicine Center  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"O.M\u00e4kitieandS.Vakkilainen \u201cCartilage\u2010Hair Hypoplasia\u2013Anauxetic Dysplasia Spectrum Disorders \u201d (2020)."},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.50"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61267"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63316"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac7041"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1072"},{"key":"e_1_2_14_9_1","unstructured":"Q. Q.Huang E. M.Wigdor P.Campbell et\u00a0al. \u201cDissecting the Contribution of Common Variants to Risk of Rare Neurodevelopmental Conditions \u201dmedRxiv (2024) 2024.03. 05.24303772."}],"container-title":["Clinical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.72355","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ccr3.72355","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.72355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T08:39:46Z","timestamp":1781253586000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ccr3.72355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":8,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ccr3.72355"],"URL":"https:\/\/doi.org\/10.1002\/ccr3.72355","archive":["Portico"],"relation":{},"ISSN":["2050-0904","2050-0904"],"issn-type":[{"value":"2050-0904","type":"print"},{"value":"2050-0904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72355"}}