{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:53:53Z","timestamp":1781650433454,"version":"3.54.5"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["20254Y0119"],"award-info":[{"award-number":["20254Y0119"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"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                      Hypotrichosis simplex (HS) is a rare form of hereditary alopecia caused by a variety of gene variants, with onset in childhood. Few studies regarding\n                      <jats:italic>LSS<\/jats:italic>\n                      -related HS(HS 14) have been reported and genotype\u2013phenotype correlations in the\n                      <jats:italic>LSS<\/jats:italic>\n                      gene are still not completely clear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we tried to make a definite diagnosis in two Chinese pediatric patients clinically suspected of congenital hypotrichosis. Peripheral blood samples of these two patients and their parents were collected and whole-exome sequencing (WES) was performed to elucidate the genetic cause. WES revealed four different compound heterozygous variants in\n                      <jats:italic>LSS<\/jats:italic>\n                      in two probands that confirmed a diagnosis HS 14, including two novel variants. AlphaFold two was performed to predict three-dimensional structures, and the PROVEAN analysis software was utilized to assess the functional changes of novel missense variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two previously reported variants,c.1054G&amp;gt;A; p.(Gly352Arg) and c.1303C&amp;gt;T; p.(Arg435Cys) were observed and two novel heterozygous variants,c.1594G&amp;gt;C; p.(Glu532Gln) and c.1010C&amp;gt;T; p.(Pro337Leu) were found in these 2\u00a0HS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In this study, we successfully identified variants in\n                      <jats:italic>LSS<\/jats:italic>\n                      in two probands that confirmed a diagnosis of HS, including two novel variants. These findings expanded the variantal spectrum of\n                      <jats:italic>LSS<\/jats:italic>\n                      -related HS 14. Moreover, teeth dysplasia could be an associated phenotype in patient with HS 14.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1742964","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:10:44Z","timestamp":1781647844000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel variants in LSS related hypotrichosis simplex 14"],"prefix":"10.3389","volume":"17","author":[{"given":"Shengyuan","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai JiaoTong University","place":["Shanghai, China"]},{"name":"Department of Dermatology, Shanghai City Qingpu District of Zhujiajiao People\u2019s Hospital","place":["Shanghai, China"]},{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biqing","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, QuanZhou Women\u2019s and Children\u2019s Hospital","place":["Quanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yile","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai City Qingpu District of Zhujiajiao People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yueyang Hospital of Integrative Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiufang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai JiaoTong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B11","doi-asserted-by":"publisher","first-page":"1512646","DOI":"10.3389\/fped.2025.1512646","article-title":"Congenital hypotrichosis caused by compound heterozygous variants in the LSS gene in a Chinese patient with strabismus: case report","volume":"13","author":"Bao","year":"2025","journal-title":"Front. Pediatr."},{"key":"B12","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":"B13","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":"B14","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":"B15","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1007\/s12031-022-02074-y","article-title":"Expanding the phenotypic spectrum of APMR4 syndrome caused by a novel variant in LSS gene and review of literature","volume":"72","author":"Elaraby","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/cge.14348","article-title":"Novel LSS variants in alopecia and intellectual disability syndrome: new case report and clinical spectrum of LSS-related rare disease traits","volume":"104","author":"Elbendary","year":"2023","journal-title":"Clin. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1111\/pde.15320","article-title":"Non-syndromic hypotrichosis: a report of two novel variants in the LSS gene","volume":"40","author":"El Hakim","year":"2023","journal-title":"Pediatr. Dermatol."},{"key":"B18","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":"2020","journal-title":"J. Dermatol."},{"key":"B19","first-page":"37","article-title":"Expansion of phenotype of lanosterol synthase-related disease: a case report and literature review","volume":"27","author":"Ho","year":"2022","journal-title":"hong kong Journal Paediatrics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"John","year":"2021","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"782653","DOI":"10.3389\/fgene.2021.782653","article-title":"The first report of a missense variant in rfx2 causing non-syndromic tooth agenesis in a consanguineous Pakistani family","volume":"12","author":"Khan","year":"2022","journal-title":"Front. Genet."},{"key":"B20","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":"B4","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1111\/bjd.14178","article-title":"Genome-wide linkage and exome sequencing analyses identify an initiation codon mutation of KRT5 in a unique Chinese family with generalized dowling-degos disease","volume":"174","author":"Li.","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"4377","DOI":"10.1111\/jocd.16530","article-title":"Two novel mutations in LSS gene associated with hypotrichosis simplex in a Chinese family","volume":"23","author":"Linfang","year":"2024","journal-title":"J. Cosmet. Dermatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol reverses protein aggregation in cataracts","volume":"523","author":"Ling","year":"2015","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1093\/ced\/llad174","article-title":"A novel compound heterozygous variant in the LLS gene is associated with nonsyndromic hypotrichosis","volume":"48","author":"Morice-Picard","year":"2023","journal-title":"Clin. Exp. Dermatol."},{"key":"B22","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":"2020","journal-title":"J. Dermatol."},{"key":"B23","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":"B8","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":"Shengyuan","year":"2020","journal-title":"J. Dermatol."},{"key":"B9","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":"Thomas","year":"2019","journal-title":"Genet. Med."},{"key":"B24","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":"B25","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1016\/j.jid.2022.03.023","article-title":"Biallelic variants in lanosterol synthase (LSS) cause Palmoplantar Keratoderma-Congenital Alopecia Syndrome type 2","volume":"142","author":"Yang","year":"2022","journal-title":"J. Invest. Dermatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels","volume":"31","author":"Yongwook","year":"2015","journal-title":"Bioinformatics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s40246-025-00798-7","article-title":"Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review","volume":"19","author":"Zhang","year":"2025","journal-title":"Hum. Genomics"},{"key":"B27","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":"B28","doi-asserted-by":"publisher","first-page":"992190","DOI":"10.3389\/fphys.2022.992190","article-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","volume":"13","author":"Zhao","year":"2023","journal-title":"Front. Physiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/exd.14774","article-title":"Biallelic mutations in LSS in autosomal-recessive mutilating palmoplantar keratoderma","volume":"32","author":"Zhou","year":"2023","journal-title":"Exp. Dermatol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1742964\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:10:45Z","timestamp":1781647845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1742964\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":27,"alternative-id":["10.3389\/fgene.2026.1742964"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1742964","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"article-number":"1742964"}}