REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis


Bayram Y., White J. J., Elcioglu N., Cho M. T., Zadeh N., Gedikbasi A., ...Daha Fazla

AMERICAN JOURNAL OF HUMAN GENETICS, cilt.101, sa.1, ss.149-156, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 101 Sayı: 1
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.ajhg.2017.06.006
  • Dergi Adı: AMERICAN JOURNAL OF HUMAN GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.149-156
  • Marmara Üniversitesi Adresli: Evet

Özet

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor (REST) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exontruncating mutations in REST for organismal development and the association with the HGF phenotype.