{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:20:19Z","timestamp":1781691619320,"version":"3.54.5"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"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. Physiol."],"abstract":"<jats:p><jats:bold>Aim:<\/jats:bold> Hypotrichosis simplex (MIM 146520) is a rare form of monogenic hereditary alopecia. Several genes have been identified as being associated with the disease, including <jats:italic>LPAR6<\/jats:italic>, <jats:italic>LIPH<\/jats:italic>, and <jats:italic>DSG4. LSS<\/jats:italic> encoding lanosterol synthase (LSS) has been shown to cause hypotrichosis simplex, but the related mechanisms have not been elucidated to date. This study aims to find mutations in <jats:italic>LSS<\/jats:italic> from a Chinese family, among which a 21-year-old male patient and his 9-year-old sister were affected by hypotrichosis simplex.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Dermoscopy and histological analysis were used to examine patients\u2019 scalps, while exome sequencing was used to find the mutations in <jats:italic>LSS<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The hair loss was only detected on the scalp of the proband and his sister, while other ectodermal structures were normal with no systemic abnormalities. Further, the exome sequencing identified a new homozygous mutation NM_002340.6 (LSS_v001):c.812T&amp;gt;C (p.(Ile271Thr)) in the <jats:italic>LSS<\/jats:italic> gene of the proband, which was also found in his sister. In addition, a heterozygous mutation of <jats:italic>LSS<\/jats:italic> was found in their asymptomatic parents. Finally, the possible protein structure of the mutational LSS was predicted.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The hypotrichosis simplex reported here could be an autosomal recessive disease in this family. The mutation on <jats:italic>LSS<\/jats:italic> might reduce the enzyme activity of LSS, thus leading to the disease.<\/jats:p>","DOI":"10.3389\/fphys.2022.992190","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T18:11:53Z","timestamp":1673028713000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel homozygous mutation in LSS gene possibly causes hypotrichosis simplex in two siblings of a Tibetan family from the western Sichuan province of China"],"prefix":"10.3389","volume":"13","author":[{"given":"Bei","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s13555-019-0313-2","article-title":"Genetic hair disorders: A Review","volume":"9","author":"Ahmed","year":"2019","journal-title":"Dermatol Ther. (Heidelb)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1038\/s41436-019-0445-x","article-title":"Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome","volume":"21","author":"Besnard","year":"2019","journal-title":"Genet. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3900","DOI":"10.1002\/ajmg.a.62438","article-title":"Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes","volume":"185","author":"Cesarato","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1515\/jpem-2017-0101","article-title":"Congenital cataract with LSS gene mutations: A new case report","volume":"30","author":"Chen","year":"2017","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1093\/nar\/gnj031","article-title":"Nucleic acid visualization with UCSF Chimera","volume":"34","author":"Couch","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1111\/j.1365-2133.2005.06958.x","article-title":"A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp","volume":"153","author":"D\u00e1valos","year":"2005","journal-title":"Br. J. Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/jid.2009.442","article-title":"Hair growth defects in Insig-deficient mice caused by cholesterol precursor accumulation and reversed by simvastatin","volume":"130","author":"Evers","year":"2010","journal-title":"J. Invest. Dermatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"897","DOI":"10.16288\/j.yczz.17-037","article-title":"Functions of Wnt signaling pathway in hair cell differentiation and regeneration","volume":"39","author":"Fan","year":"2017","journal-title":"Yi Chuan"},{"key":"B9","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1111\/1346-8138.15697","article-title":"Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene","volume":"48","author":"Hua","year":"2021","journal-title":"J. Dermatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1126\/science.1133276","article-title":"Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH","volume":"314","author":"Kazantseva","year":"2006","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/s0092-8674(03)00273-3","article-title":"Desmoglein 4 in hair follicle differentiation and epidermal adhesion: Evidence from inherited hypotrichosis and acquired pemphigus vulgaris","volume":"113","author":"Kljuic","year":"2003","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/ng1163","article-title":"Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin","volume":"34","author":"Levy-Nissenbaum","year":"2003","journal-title":"Nat. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e393","DOI":"10.1111\/1346-8138.15010","article-title":"A novel and a known mutation in LSS gene associated with hypotrichosis 14 in a Chinese family","volume":"46","author":"Li","year":"2019","journal-title":"J. Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1172\/JCI20797","article-title":"Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat","volume":"116","author":"Mori","year":"2006","journal-title":"J. Clin. Invest."},{"key":"B15","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1111\/1346-8138.15679","article-title":"Two cases of severe congenital hypotrichosis caused by compound heterozygous mutations in the LSS gene","volume":"48","author":"Murata","year":"2021","journal-title":"J. Dermatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/S0194-5998(98)70167-6","article-title":"Contribution of membrane cholesterol to outer hair cell lateral wall stiffness","volume":"119","author":"Nguyen","year":"1998","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/ng.84","article-title":"G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth","volume":"40","author":"Pasternack","year":"2008","journal-title":"Nat. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.ajhg.2018.09.011","article-title":"Bi-Allelic mutations in LSS, encoding lanosterol synthase, cause autosomal-recessive hypotrichosis simplex","volume":"103","author":"Romano","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/nature08875","article-title":"APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex","volume":"464","author":"Shimomura","year":"2010","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e1008628","DOI":"10.1371\/journal.pgen.1008628","article-title":"Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice","volume":"16","author":"Wada","year":"2020","journal-title":"PLoS Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol reverses protein aggregation in cataracts","volume":"523","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"788422","DOI":"10.3389\/fcell.2021.788422","article-title":"Defect of LSS disrupts lens development in cataractogenesis","volume":"9","author":"Zhao","year":"2021","journal-title":"Front. Cell Dev. Biol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.992190\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T18:11:56Z","timestamp":1673028716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.992190\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":22,"alternative-id":["10.3389\/fphys.2022.992190"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.992190","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]},"article-number":"992190"}}