Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review

Abstract Background Congenital hypotrichosis 14 is a nonsyndromic form of alopecia associated with pathogenic variants in the lanosterol synthase (LSS) gene. Recent studies have expanded the spectrum of LSS-related phenotypes, including congenital cataracts, alopecia-intellectual disability syndrome...

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Main Authors: Yujing Zhang, Mengxi Zhao, Xiangqian Li, Yongping Zhao, Yijie Sun, Jianzhong Zhang, Cong Yu, Cheng Zhou
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Human Genomics
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Online Access:https://doi.org/10.1186/s40246-025-00798-7
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author Yujing Zhang
Mengxi Zhao
Xiangqian Li
Yongping Zhao
Yijie Sun
Jianzhong Zhang
Cong Yu
Cheng Zhou
author_facet Yujing Zhang
Mengxi Zhao
Xiangqian Li
Yongping Zhao
Yijie Sun
Jianzhong Zhang
Cong Yu
Cheng Zhou
author_sort Yujing Zhang
collection DOAJ
description Abstract Background Congenital hypotrichosis 14 is a nonsyndromic form of alopecia associated with pathogenic variants in the lanosterol synthase (LSS) gene. Recent studies have expanded the spectrum of LSS-related phenotypes, including congenital cataracts, alopecia-intellectual disability syndrome, and palmoplantar keratoderma. Currently, investigations into this disease are still limited, and its treatment remains elusive. Methods In this study, we aimed to report six Chinese patients who were diagnosed with hypotrichosis 14, whose conditions were attributed to five novel and recurrent variants in the LSS gene identified via whole exome sequencing. Moreover, the reported LSS gene has also been summarized. Results We described six patients in five Chinese families with hair loss, and one of whom had a rare accompanying phenotype of hypergonadotropic hypogonadism, which has rarely been reported. Five novel variants were discovered in the LSS gene, including c.919_921del (p.His307del), c.1987 C > T (p.Arg663Trp), c.982 C > T (p.Arg328*), c.1405_1407del (p.Glu469del) and c.193_200dup (p.Pro68Argfs*14). Conclusions Our comprehensive summary of phenotypes caused by LSS gene variants not only enriches the existing knowledge on congenital hypotrichosis 14 but also provides crucial guidance for more accurate genetic counseling and potentially new directions for future research in understanding the disease mechanism and developing targeted therapies.
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spelling doaj-art-e44d616acb284f32aa131c21dc7beb072025-08-20T03:43:20ZengBMCHuman Genomics1479-73642025-07-0119111010.1186/s40246-025-00798-7Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature reviewYujing Zhang0Mengxi Zhao1Xiangqian Li2Yongping Zhao3Yijie Sun4Jianzhong Zhang5Cong Yu6Cheng Zhou7Department of Dermatology, Peking University People’s HospitalDepartment of Dermatology, Peking University People’s HospitalDepartment of Dermatology, Peking University People’s HospitalReproductive Medicine Center, Peking University People’s HospitalDepartment of Dermatology, Peking University People’s HospitalDepartment of Dermatology, Peking University People’s HospitalDepartment of Dermatology, Peking University People’s HospitalDepartment of Dermatology, Peking University People’s HospitalAbstract Background Congenital hypotrichosis 14 is a nonsyndromic form of alopecia associated with pathogenic variants in the lanosterol synthase (LSS) gene. Recent studies have expanded the spectrum of LSS-related phenotypes, including congenital cataracts, alopecia-intellectual disability syndrome, and palmoplantar keratoderma. Currently, investigations into this disease are still limited, and its treatment remains elusive. Methods In this study, we aimed to report six Chinese patients who were diagnosed with hypotrichosis 14, whose conditions were attributed to five novel and recurrent variants in the LSS gene identified via whole exome sequencing. Moreover, the reported LSS gene has also been summarized. Results We described six patients in five Chinese families with hair loss, and one of whom had a rare accompanying phenotype of hypergonadotropic hypogonadism, which has rarely been reported. Five novel variants were discovered in the LSS gene, including c.919_921del (p.His307del), c.1987 C > T (p.Arg663Trp), c.982 C > T (p.Arg328*), c.1405_1407del (p.Glu469del) and c.193_200dup (p.Pro68Argfs*14). Conclusions Our comprehensive summary of phenotypes caused by LSS gene variants not only enriches the existing knowledge on congenital hypotrichosis 14 but also provides crucial guidance for more accurate genetic counseling and potentially new directions for future research in understanding the disease mechanism and developing targeted therapies.https://doi.org/10.1186/s40246-025-00798-7Hypotrichosis 14AlopeciaLSSGenePathogenic variantsLanosterol synthase
spellingShingle Yujing Zhang
Mengxi Zhao
Xiangqian Li
Yongping Zhao
Yijie Sun
Jianzhong Zhang
Cong Yu
Cheng Zhou
Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
Human Genomics
Hypotrichosis 14
Alopecia
LSS
Gene
Pathogenic variants
Lanosterol synthase
title Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
title_full Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
title_fullStr Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
title_full_unstemmed Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
title_short Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
title_sort hypotrichosis 14 novel variants of the lss gene in five chinese families and insights from literature review
topic Hypotrichosis 14
Alopecia
LSS
Gene
Pathogenic variants
Lanosterol synthase
url https://doi.org/10.1186/s40246-025-00798-7
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