{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:11:08Z","timestamp":1790223068493,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019370","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019370","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Boucher\u2013Neuh\u00e4user syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the <jats:italic>PNPLA6<\/jats:italic> gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of BNS, genetic validation, and a systematic review of <jats:italic>PNPLA6<\/jats:italic> variants related to BNS.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Clinical data and blood samples were collected from the patient and their parents, and whole-exome sequencing was performed and confirmed by Sanger sequencing. RNA-sequencing (RNA-Seq) and quantitative RT-PCR (qRT-PCR) were performed, and the three-dimensional protein structures of the variants were predicted.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We report a 17-year-old female with progressive night blindness since the age of four, primary amenorrhea, and non-development of secondary sexual characteristics. Her impaired vision was diagnosed as retinal pigmentary degeneration of the retina. She had congenital hypogonadotropic hypogonadism (CHH) but no cerebellar ataxia at present. Two novel compound heterozygous variants (c.2241del\/p.Met748TrpfsTer65 and c.2986A&amp;gt;G\/p.Thr996Ala) of the <jats:italic>PNPLA6<\/jats:italic> gene (NM_006702.4) were identified by whole-exome sequencing. The former variant was carried from her healthy father and has not been reported previously. The latter was inherited from her healthy mother and was noted in a report without functional studies. The RT-PCR results showed that the mRNA expression of <jats:italic>PNPLA6<\/jats:italic> was lower in this patient and her father than in the control group. She was diagnosed with BNS. Both variants (c.2241del and c.2986A&amp;gt;G) were likely pathogenic according to the ACMG criteria. The novel variants in the <jats:italic>PNPLA6<\/jats:italic> gene related to Boucher\u2013Neuh\u00e4user syndrome were summarized in this article.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The possibility of Boucher\u2013Neuh\u00e4user syndrome should be considered when patients present with night blindness, impaired vision, and hypogonadotropic hypogonadism. Gene sequencing is currently the primary diagnostic method. Herein, novel compound heterozygous variants of <jats:italic>PNPLA6<\/jats:italic> were identified in a BNS patient, and its function was verified at the RNA level. The <jats:italic>PNPLA6<\/jats:italic> c.2241del variant is novel and potentially pathogenic, expanding the mutation spectrum in <jats:italic>PNPLA6<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fgene.2022.810537","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T12:12:01Z","timestamp":1644235921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher\u2013Neuh\u00e4user Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Junyu","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanghong","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1600-0404.1969.tb01261.x","article-title":"Familial Ataxia, Hypogonadism and Retinal Degeneration","volume":"45","author":"Boucher","year":"1969","journal-title":"Acta Neurol. 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