{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:09:03Z","timestamp":1791486543496,"version":"4.3.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA) is a rare syndromic disorder characterized by global neurodevelopmental delay, early-onset hypotonia, poor overall growth, poor speech\/language ability, and additional common phenotypes such as eye anomalies, joint hypermobility, and skeletal anomalies of the hands and feet. NEDDFSA is caused by heterozygous pathogenic variants in the <jats:italic>ZMIZ1<\/jats:italic> gene on chromosome 10q22.3 with autosomal dominant (AD) mode of inheritance. All the 32 reported cases with variants in <jats:italic>ZMIZ1<\/jats:italic> gene had a genetic background in Caucasian, Hispanic, North African, and Southeastern Asian. Until now, there are no reports of Chinese patients with <jats:italic>ZMIZ1<\/jats:italic> pathogenic variants.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A 5-year-old girl was found to have the characteristic phenotypes of NEDDFSA. Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for the trio of this female patient. Sanger sequencing was used to verify the selected variants. A comprehensive molecular analysis was carried out by protein structure prediction, evolutionary conservation, motif scanning, tissue-specific expression, and protein interaction network to elucidate pathogenicity of the identified ZMIZ1 variants.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The karyotype was 46, XX with no micro-chromosomal abnormalities identified by array-CGH. There were 20 variants detected in the female patient by WES. A <jats:italic>de novo<\/jats:italic> heterozygous missense variant (c.2330G &amp;gt; A, p.Gly777Glu, G777E) was identified in the exon 20 of <jats:italic>ZMIZ1<\/jats:italic>. No variants of <jats:italic>ZMIZ1<\/jats:italic> were identified in the non-consanguineous parents and her healthy elder sister. It was predicted that G777E was pathogenic and detrimental to the spatial conformation of the MIZ\/SP-RING zinc finger domain of ZMIZ1.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Thus far, only four scientific articles reported deleterious variants in <jats:italic>ZMIZ1<\/jats:italic> and most of the cases were from Western countries. This is the first report about a Chinese patient with <jats:italic>ZMIZ1<\/jats:italic> variant. It will broaden the current knowledge of ZMIZ1 variants and variable clinical presentations for clinicians and genetic counselors.<\/jats:p>","DOI":"10.3389\/fgene.2022.840577","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T10:15:24Z","timestamp":1648721724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["A de Novo ZMIZ1 Pathogenic Variant for Neurodevelopmental Disorder With Dysmorphic Facies and Distal Skeletal Anomalies"],"prefix":"10.3389","volume":"13","author":[{"given":"Guanting","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binqiang","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyun","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuwu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongling","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A Method and Server for Predicting Damaging Missense Mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. 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