Exome sequencing identifies a SREBF1 recurrent ARG557CYS mutation as the cause of hereditary mucoepithelial dysplasia in a family with high clinical variability

Am J Med Genet A. 2020 Nov;182(11):2773-2777. doi: 10.1002/ajmg.a.61849. Epub 2020 Sep 9.


Hereditary mucoepithelial dysplasia (HMD) is an uncommon autosomal dominant disease affecting skin, mucosae, hair, eyes, and lungs. Prominent clinical features include non-scarring alopecia, mucosal erythema, perineal erythematous intertrigo, and involvement of the conjunctival mucosa. To date, 20 familial or sporadic HMD cases have been described, most of them originating from Caucasian ethnic groups. In this study, a novel HMD pedigree, including an affected father and his daughter, is reported. Clinical expression showed significant differences in affected subjects, especially in the distribution and severity of skin lesions. Exome sequencing demonstrated that both affected subjects carried a heterozygous c.1669C>T (p.Arg557Cys) pathogenic variant in the SREBF1 gene. Our results improve the knowledge of the clinical and genetic features of HMD. In addition, a comparative review of the clinical features of all published HMD cases is presented.

Keywords: SREBF1; corneal vascularization; genodermatosis; hereditary mucoepithelial dysplasia; psoriasiform lesions.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alopecia / genetics
  • Alopecia / pathology*
  • Child
  • Exome Sequencing / methods*
  • Female
  • Heterozygote
  • Humans
  • Keratosis / genetics
  • Keratosis / pathology*
  • Male
  • Mucous Membrane / pathology
  • Mutation*
  • Pedigree
  • Phenotype*
  • Skin Abnormalities / genetics
  • Skin Abnormalities / pathology*
  • Sterol Regulatory Element Binding Protein 1 / genetics*


  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1

Supplementary concepts

  • Urban Schosser Spohn syndrome