{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:20:24Z","timestamp":1782991224657,"version":"3.54.5"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"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>The <jats:italic>SMPD4<\/jats:italic> gene encodes sphingomyelin phosphodiesterase 4, which preferentially hydrolyzes sphingomyelin over other phospholipids. The biallelic loss-of-function variants of <jats:italic>SMPD4<\/jats:italic> have been identified in a group of children with neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA). Here, we report a girl of Chinese ancestry with intrauterine growth restriction, microcephaly, postnatal developmental delay, arthrogryposis, hypertonicity, seizure, and hypomyelination on brain magnetic resonance imaging; biallelic null variants (c.1347C &amp;gt; G [p.Tyr449*]; Chr2 [GRCh37]: g.130877574_131221737del [whole-gene deletion]) were detected by whole-exome sequencing. Our case is the first report of NEDMABA of Chinese ancestry, confirming the involvement of <jats:italic>SMPD4<\/jats:italic> in NEDMABA and expanding the mutation spectrum of this syndrome.<\/jats:p>","DOI":"10.3389\/fgene.2022.872264","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T08:38:12Z","timestamp":1652690292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: Novel Biallelic Null Variants of SMPD4 Confirm Its Involvement in Neurodevelopmental Disorder With Microcephaly, Arthrogryposis, and Structural Brain Anomalies"],"prefix":"10.3389","volume":"13","author":[{"given":"Weigang","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtian","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.3174\/ajnr.A2440","article-title":"Congenital Microcephaly with a Simplified Gyral Pattern: Associated Findings and Their Significance","volume":"32","author":"Adachi","year":"2011","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1093\/nar\/gku345","article-title":"CANOES: Detecting Rare Copy Number Variants from Whole Exome Sequencing Data","volume":"42","author":"Backenroth","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.pharep.2015.12.008","article-title":"Regulation of Sphingomyelin Metabolism","volume":"68","author":"Bienias","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"449.e1","DOI":"10.1016\/j.ajog.2015.08.032","article-title":"Racial\/Ethnic Standards for Fetal Growth: The NICHD Fetal Growth Studies","volume":"213","author":"Buck Louis","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"7.23.1","DOI":"10.1002\/0471142905.hg0723s81","article-title":"Using XHMM Software to Detect Copy Number Variation in Whole\u2010Exome Sequencing Data","volume":"81","author":"Fromer","year":"2014","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1038\/s41436-019-0472-7","article-title":"Estimating Yields of Prenatal Carrier Screening and Implications for Design of Expanded Carrier Screening Panels","volume":"21","author":"Guo","year":"2019","journal-title":"Genet. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"13784","DOI":"10.1074\/jbc.M511306200","article-title":"Novel Tumor Necrosis Factor-Responsive Mammalian Neutral Sphingomyelinase-3 Is a C-Tail-Anchored Protein","volume":"281","author":"Krut","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and Accurate Long-Read Alignment with Burrows-Wheeler Transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.ajhg.2019.08.006","article-title":"Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis","volume":"105","author":"Magini","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce Framework for Analyzing Next-Generation DNA Sequencing Data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e173438","DOI":"10.1001\/jamapediatrics.2017.3438","article-title":"Use of Exome Sequencing for Infants in Intensive Care Units","volume":"171","author":"Meng","year":"2017","journal-title":"JAMA Pediatr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.ajhg.2019.04.01110.1016\/j.ajhg.2019.09.019","article-title":"Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population","volume":"105","author":"Monies","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX : Structure Visualization for Researchers, Educators, and Developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1136\/jmedgenet-2020-106901","article-title":"Neurogenetic Fetal Akinesia and Arthrogryposis: Genetics, Expanding Genotype-Phenotypes and Functional Genomics","volume":"58","author":"Ravenscroft","year":"2020","journal-title":"J. Med. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e1004873","DOI":"10.1371\/journal.pcbi.1004873","article-title":"CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing","volume":"12","author":"Talevich","year":"2016","journal-title":"Plos Comput. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively Expanding the Structural Coverage of Protein-Sequence Space with High-Accuracy Models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional Annotation of Genetic Variants from High-Throughput Sequencing Data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders","volume":"369","author":"Yang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e98","DOI":"10.1002\/cphg.98","article-title":"Clinical Interpretation of Sequence Variants","volume":"106","author":"Zhang","year":"2020","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e59569","DOI":"10.1371\/journal.pone.0059569","article-title":"Construction of a New Growth References for China Based on Urban Chinese Children: Comparison with the WHO Growth Standards","volume":"8","author":"Zong","year":"2013","journal-title":"PLoS One"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.872264\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T08:38:15Z","timestamp":1652690295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.872264\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,16]]},"references-count":22,"alternative-id":["10.3389\/fgene.2022.872264"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.872264","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,16]]},"article-number":"872264"}}