{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:33Z","timestamp":1753869693526,"version":"3.41.2"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune skeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an extremely rare, autosomal recessive genetic disorder characterized by various skeletal abnormalities, neurodevelopmental deficits, and abnormal immune system function. ISDNA is caused by variation in the exostosin\u2010like 3 (<jats:italic>EXTL3<\/jats:italic>) gene, located on chromosome 8p21.2, whose primary function is the biosynthesis of heparan sulfate (HS) skeleton structure. Only a few variations in the <jats:italic>EXTL3<\/jats:italic> gene have been discovered so far. In these years of development, many pathogenic variants in genetic diseases with genetic and phenotypic heterogeneity have been investigated using whole\u2010exome sequencing (WES) technology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this research, a novel <jats:italic>EXTL3<\/jats:italic> variant was first detected in a patient using WES, which was validated from Sanger sequencing in this family. Family history and clinical information were then collected through comprehensive medical examinations and genetic counseling. In silico prediction was then utilized to confirm the pathogenicity of the variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel homozygous variant, NM_001440: c.2015G&gt;A (p.Arg672Gln) in the <jats:italic>EXTL3<\/jats:italic> gene, was identified using WES, which has never been reported before. Sanger sequencing was performed to confirm that the variant segregated with the disease within the family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This research identified a novel pathogenic variant in the <jats:italic>EXTL3<\/jats:italic> gene responsible for ISDNA in a Chinese family. It showed the potential diagnostic role of WES in ISDNA, expanded the <jats:italic>EXTL3<\/jats:italic> gene variation spectrum, and demonstrated that the diagnosis of ISDNA using WES is feasible and effective. More comprehensive genetic counseling and precise prenatal diagnosis for the next pregnancy can also be provided to families with genetic disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2308","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:37:22Z","timestamp":1701131842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune skeletal dysplasia with neurodevelopmental abnormalities caused by a novel variant of <i>EXTL3<\/i> gene in a Chinese family"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-5288","authenticated-orcid":false,"given":"Xinyuan","family":"Tian","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Gansu Provincial Maternity and Child Care Hospital, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases  Lanzhou China"},{"name":"School of Public Health Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Early Childhood Development Gansu Provincial Maternity and Child\u2010Care Hospital  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Gansu Provincial Maternity and Child Care Hospital, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Gansu Provincial Maternity and Child Care Hospital, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases  Lanzhou 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