Publication

Keratosis Follicularis Spinulosa Decalvans Is Caused by Mutations in MBTPS2

Aten, E., Brasz, L. C., Bornholdt, D., Hooijkaas, I. B., Porteous, M. E., Sybert, V. P., Vermeer, M. H., Vossen, R. H. A. M., van der Wielen, M. J. R., Bakker, E., Breuning, M. H., Grzeschik, K-H., Oosterwijk, J. C. & den Dunnen, J. T., Oct-2010, In : Human Mutation. 31, 10, p. 1125-1133 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Emmelien Aten
  • Lisa C. Brasz
  • Dorothea Bornholdt
  • Ingeborg B. Hooijkaas
  • Mary E. Porteous
  • Virginia P. Sybert
  • Maarten H. Vermeer
  • Rolf H. A. M. Vossen
  • Michiel J. R. van der Wielen
  • Egbert Bakker
  • Martijn H. Breuning
  • Karl-Heinz Grzeschik
  • Jan C. Oosterwijk
  • Johan T. den Dunnen

Keratosis Follicularis Spinulosa Decalvans (KFSD) is a rare genetic disorder characterized by development of hyperkeratotic follicular papules on the scalp followed by progressive alopecia of the scalp, eyelashes, and eyebrows. Associated eye findings include photophobia in childhood and corneal dystrophy. Due to the genetic and clinical heterogeneity of similar disorders, a definitive diagnosis of KFSD is often challenging. Toward identification of the causative gene we reanalyzed a large Dutch KFSD family. SNP arrays (1 M) redefined the locus to a 2.9-Mb region at Xp22.12-Xp22.11. Screening of all 14 genes in the candidate region identified MBTPS2 as the candidate gene carrying a c.1523A>G (p.Asn508Ser) missense mutation. The variant was also identified in two unrelated X-linked KFSD families and cosegregated with KFSD in all families. In symptomatic female carriers, skewed X-inactivation of the normal allele matched with increased severity of symptoms. MBTPS2 is required for cleavage of sterol regulatory element-binding proteins (SREBPs). In vitro functional expression studies of the c. 1523A>G mutation showed that sterol responsiveness was reduced by half. Other missense mutations in MBTPS2 have recently been identified in patients with IFAP syndrome. We postulate that both phenotypes are in the spectrum of one genetic disorder with a partially overlapping phenotype. Hum Mutat 31:1125-1133, 2010. (C) 2010 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)1125-1133
Number of pages9
JournalHuman Mutation
Volume31
Issue number10
Publication statusPublished - Oct-2010

    Keywords

  • Keratosis Follicularis Spinulosa Decalvans, MBTPS2, IFAP, ichthyosis follicularis, X-LINKED ICHTHYOSIS, GENETIC-HETEROGENEITY, PILARIS ATROPHICANS, DISEASE, FAMILY, XP22.13-P22.2, LOCALIZATION, CONFIRMATION, INHERITANCE, REFINEMENT

ID: 5177923