A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome

Orphanet Journal of Rare Diseases

Omid Zargari¹  Jouni Uitto²  Amir Hossein Saeidian²  Hassan Vahidnezhad²  Leila Youssefian²  Andrew Touati²  Sirous Zeinali³ 

[1] Dana Clinic;Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University;Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran;

关键词: Ichthyosis;    Hypotrichosis;    Ichthyosis-hypotrichosis syndrome;    ST14;    Matriptase;    Next-generation sequencing;   

DOI  :  10.1186/s13023-017-0728-8

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown