{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:44:16Z","timestamp":1791229456681,"version":"4.1.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Oliver-McFarlane syndrome (OMCS) is an extremely rare congenital disorder that presents with hypogonadotropic hypogonadism, long eyelashes and eyebrows, pigmentary retinopathy, peripheral nerve axon neuropathy and other associated features. It is currently known that OMCS is linked to variants in the patatin-like phospholipase domain containing 6 (\n                      <jats:italic>PNPLA6<\/jats:italic>\n                      ) gene, but the specific pathogenic mechanism is still unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed Whole exome sequencing (WES) on the proband and his parents, followed by validation of the findings through Sanger sequencing and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sanger sequencing identified two compound heterozygous variants in the\n                      <jats:italic>PNPLA6<\/jats:italic>\n                      (NM_006702.5) gene in the proband: c.3184G&amp;gt;A (p.Val1062Met) and c.2704-18C&amp;gt;G. According to the ACMG guidelines, the c.3184G&amp;gt;A variant is classified as likely pathogenic, while the c.2704-18C&amp;gt;G variant is discovered for the first time. Segregation analysis further revealed that the c.3184G&amp;gt;A variant was inherited from the father, whereas the c.2704-18C&amp;gt;G variant was derived from the mother\u2014consistent with an autosomal recessive inheritance pattern. RT-PCR detected that the c.2704-18C&amp;gt;G variant caused a 29bp deletion upstream of exon 26, resulting in a splice site mutation (p.His902Alafs108).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We report a case from China of\n                      <jats:italic>PNPLA6<\/jats:italic>\n                      gene variants leading to Oliver-McFarlane syndrome, with the patient exhibiting typical characteristics of OMCS. Our findings further substantiate the pathogenicity of\n                      <jats:italic>PNPLA6<\/jats:italic>\n                      gene variation in OMCS, broadening the established genotypic spectrum of the\n                      <jats:italic>PNPLA6<\/jats:italic>\n                      gene. These findings enhance the understanding of its pathogenesis and offer perspectives for clinical diagnosis and management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2025.1660243","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T22:10:26Z","timestamp":1762380626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Novel compound heterozygous mutations in PNPLA6 gene associated with Oliver-McFarlane syndrome"],"prefix":"10.3389","volume":"16","author":[{"given":"Jia","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"848","DOI":"10.3390\/biom9120848","article-title":"Characterization of the interaction of neuropathy target esterase with the endoplasmic reticulum and lipid droplets","volume":"9","author":"Chang","year":"2019","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1007\/s00415-014-7516-3","article-title":"Compound heterozygous PNPLA6 mutations cause boucher\u2013neuh\u00e4user syndrome with late-onset ataxia","volume":"261","author":"Deik","year":"2014","journal-title":"J. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1038\/s41431-021-00959-x","article-title":"The LOVD3 platform: efficient genome-wide sharing of genetic variants","volume":"29","author":"Fokkema","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1136\/jmedgenet-2014-102856","article-title":"Neuropathy target esterase impairments cause oliver\u2013McFarlane and laurence\u2013moon syndromes","volume":"52","author":"Hufnagel","year":"2015","journal-title":"J. Med. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1080\/13816810.2021.1904419","article-title":"Oliver McFarlane syndrome: two new cases and a review of the literature","volume":"42","author":"Lisbjerg","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1080\/13816810.2023.2254830","article-title":"PNPLA6 disorders: what\u2019s in a name?","volume":"44","author":"Liu","year":"2023","journal-title":"Ophthalmic Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1093\/brain\/awae055","article-title":"Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders","volume":"147","author":"Liu","year":"2024","journal-title":"Brain J. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1128\/MCB.24.4.1667-1679.2004","article-title":"Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice","volume":"24","author":"Moser","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1001\/archopht.1965.00970040171008","article-title":"Congenital trichomegaly: with associated pigmentary degeneration of the retina, dwarfism, and mental retardation","volume":"74","author":"Oliver","year":"1965","journal-title":"Arch. Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s00204-010-0518-8","article-title":"Expression of neuropathy target esterase in mouse embryonic stem cells during differentiation","volume":"84","author":"Pamies","year":"2010","journal-title":"Arch. Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.neuroscience.2014.08.031","article-title":"Silencing of PNPLA6, the neuropathy target esterase (NTE) codifying gene, alters neurodifferentiation of human embryonal carcinoma stem cells (NT2)","volume":"281","author":"Pamies","year":"2014","journal-title":"Neuroscience"},{"key":"B12","doi-asserted-by":"publisher","first-page":"D221","DOI":"10.1093\/nar\/gkx1031","article-title":"Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation","volume":"46","author":"Pujar","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"11594","DOI":"10.1523\/JNEUROSCI.3007-09.2009","article-title":"Neuropathy target esterase is required for adult vertebrate axon maintenance","volume":"29","author":"Read","year":"2009","journal-title":"J. Neurosci."},{"key":"B14","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":"B15","doi-asserted-by":"publisher","first-page":"484","DOI":"10.3760\/cma.j.cn112142-20220627-00316","article-title":"A case of oliver-McFarlane syndrome caused by PNPLA6 gene mutation","volume":"59","author":"Shi","year":"2023","journal-title":"Zhonghua Yan Ke Za Zhi Chin. J. Ophthalmol."},{"key":"B16","article-title":"PNPLA6 disorders","volume-title":"GeneReviews\u00ae","author":"Synofzik","year":"1993"},{"key":"B17","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1093\/brain\/awt326","article-title":"PNPLA6 mutations cause boucher-neuhauser and gordon holmes syndromes as part of a broad neurodegenerative spectrum","volume":"137","author":"Synofzik","year":"2014","journal-title":"Brain"},{"key":"B18","doi-asserted-by":"publisher","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"E2067","DOI":"10.1210\/jc.2014-1836","article-title":"Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in gordon holmes syndrome","volume":"99","author":"Topaloglu","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B20","doi-asserted-by":"publisher","first-page":"20942","DOI":"10.1074\/jbc.M200330200","article-title":"Human neuropathy target esterase catalyzes hydrolysis of membrane lipids","volume":"277","author":"Van Tienhoven","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"108327","DOI":"10.1016\/j.exer.2020.108327","article-title":"Novel variants in PNPLA6 causing syndromic retinal dystrophy","volume":"202","author":"Wu","year":"2021","journal-title":"Exp. Eye Res."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1660243\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:29:39Z","timestamp":1762428579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1660243\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":21,"alternative-id":["10.3389\/fgene.2025.1660243"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1660243","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"article-number":"1660243"}}