{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:38:22Z","timestamp":1770957502729,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mitochondrial complex\u2010I deficiency, nuclear type 16, is a rare autosomal recessive disorder caused by biallelic pathogenic variants in <jats:italic>NDUFAF5<\/jats:italic> (<jats:italic>C20orf7<\/jats:italic>) (OMIM 618238). The aim of this study was to describe a severe early prenatal manifestation of this disorder, which was previously considered to occur only postnatally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a multicenter retrospective case series including five fetuses from three non\u2010related families, which shared common sonographic abnormalities, including brain cysts, corpus callosal malformations, non\u2010immune hydrops fetalis and growth restriction. Genetic evaluation included chromosomal microarray analysis and exome sequencing. Two fetuses from the same family were also available for pathology examination, including electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chromosomal microarray analysis revealed no chromosomal abnormality in any of the tested cases. Trio exome sequencing demonstrated that three affected fetuses from three unrelated families were compound heterozygous or homozygous for likely pathogenic variants in <jats:italic>NDUFAF5<\/jats:italic>. No other causative variants were detected. The association between <jats:italic>NDUFAF5<\/jats:italic> variants and fetal malformations was further confirmed by segregation analysis. Histological evaluation of fetal tissues and electron microscopy of the skeletal muscle, liver, proximal tubules and heart demonstrated changes that resembled postmortem findings in patients with mitochondrial depletion disorders as well as previously undescribed findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mitochondrial complex\u2010I deficiency and specifically biallelic mutations in <jats:italic>NDUFAF5<\/jats:italic> have a role in abnormal fetal development, presenting with severe congenital malformations. Mitochondrial complex\u2010I disorders should be considered in the differential diagnosis of corpus callosal malformations and brain cysts, especially when associated with extracranial abnormalities, such as fetal growth restriction and non\u2010immune hydrops fetalis. \u00a9 2023 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.27482","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T03:13:11Z","timestamp":1695006791000},"page":"392-398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Unique prenatal manifestations of biallelic <scp><i>NDUFAF5<\/i><\/scp> variants: expansion of phenotype"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7667-2634","authenticated-orcid":false,"given":"D.","family":"Brabbing\u2010Goldstein","sequence":"first","affiliation":[{"name":"Raphael Recanati 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