A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome
Abstract Background Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular a...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-017-0728-8 |
| _version_ | 1819177284686315520 |
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| author | Leila Youssefian Andrew Touati Amir Hossein Saeidian Omid Zargari Sirous Zeinali Hassan Vahidnezhad Jouni Uitto |
| author_facet | Leila Youssefian Andrew Touati Amir Hossein Saeidian Omid Zargari Sirous Zeinali Hassan Vahidnezhad Jouni Uitto |
| author_sort | Leila Youssefian |
| collection | DOAJ |
| description | Abstract Background Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However, the understanding of the specific consequences of mutations in ST14 on the development of this syndrome is incomplete. Results Using a targeted next-generation sequencing array of 38 ichthyosis-associated genes on a large cohort of 180 ichthyosis patients from a primarily consanguineous background, a previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a patient with IHS. This mutation affects an essential site within a ligand-binding domain of matriptase. Comparison with previous reports of IHS allowed further delineation of the phenotype of IHS in correlation with mutations present in these patients. Histological and ultrastructural analysis of skin and hair identified novel features in this disorder. Conclusions This study correlates genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum of pathology associated with the disorder, and provides clinical evidence of the importance of the Asp482 amino acid, previously shown to have an essential role in matriptase activation. |
| first_indexed | 2024-12-22T21:24:13Z |
| format | Article |
| id | doaj.art-d41b368c2e734e9e881e891c2ad783bd |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-22T21:24:13Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-d41b368c2e734e9e881e891c2ad783bd2022-12-21T18:12:06ZengBMCOrphanet Journal of Rare Diseases1750-11722017-12-011211710.1186/s13023-017-0728-8A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndromeLeila Youssefian0Andrew Touati1Amir Hossein Saeidian2Omid Zargari3Sirous Zeinali4Hassan Vahidnezhad5Jouni Uitto6Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDana ClinicMolecular Medicine Department, Biotechnology Research Center, Pasteur Institute of IranDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityAbstract Background Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However, the understanding of the specific consequences of mutations in ST14 on the development of this syndrome is incomplete. Results Using a targeted next-generation sequencing array of 38 ichthyosis-associated genes on a large cohort of 180 ichthyosis patients from a primarily consanguineous background, a previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a patient with IHS. This mutation affects an essential site within a ligand-binding domain of matriptase. Comparison with previous reports of IHS allowed further delineation of the phenotype of IHS in correlation with mutations present in these patients. Histological and ultrastructural analysis of skin and hair identified novel features in this disorder. Conclusions This study correlates genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum of pathology associated with the disorder, and provides clinical evidence of the importance of the Asp482 amino acid, previously shown to have an essential role in matriptase activation.http://link.springer.com/article/10.1186/s13023-017-0728-8IchthyosisHypotrichosisIchthyosis-hypotrichosis syndromeST14MatriptaseNext-generation sequencing |
| spellingShingle | Leila Youssefian Andrew Touati Amir Hossein Saeidian Omid Zargari Sirous Zeinali Hassan Vahidnezhad Jouni Uitto A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome Orphanet Journal of Rare Diseases Ichthyosis Hypotrichosis Ichthyosis-hypotrichosis syndrome ST14 Matriptase Next-generation sequencing |
| title | A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome |
| title_full | A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome |
| title_fullStr | A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome |
| title_full_unstemmed | A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome |
| title_short | A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome |
| title_sort | novel mutation in st14 at a functionally significant amino acid residue expands the spectrum of ichthyosis hypotrichosis syndrome |
| topic | Ichthyosis Hypotrichosis Ichthyosis-hypotrichosis syndrome ST14 Matriptase Next-generation sequencing |
| url | http://link.springer.com/article/10.1186/s13023-017-0728-8 |
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