Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A catalog of genetic loci associated with kidney function from analyses of a million individuals

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Publisher Correction: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Haploinsufficiency of ARHGAP42 is associated with hypertension

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. von Hippel-Lindau development in children and adolescents

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Familial craniofacial abnormality and polymicrogyria associated with a microdeletion affecting the NFIA gene

    Research output: Contribution to journalJournal articleResearchpeer-review

  • DDD Study
  • M Felicia Basilicata
  • Ange-Line Bruel
  • Giuseppe Semplicio
  • Claudia Isabelle Keller Valsecchi
  • Tuğçe Aktaş
  • Yannis Duffourd
  • Tobias Rumpf
  • Jenny Morton
  • Iben Bache
  • Witold G Szymanski
  • Christian Gilissen
  • Olivier Vanakker
  • Katrin Õunap
  • Gerhard Mittler
  • Ineke van der Burgt
  • Salima El Chehadeh
  • Megan T Cho
  • Rolph Pfundt
  • Tiong Yang Tan
  • Maria Kirchhoff
  • Björn Menten
  • Sarah Vergult
  • Kristin Lindstrom
  • André Reis
  • Diana S Johnson
  • Alan Fryer
  • Victoria McKay
  • Richard B Fisher
  • Christel Thauvin-Robinet
  • David Francis
  • Tony Roscioli
  • Sander Pajusalu
  • Kelly Radtke
  • Jaya Ganesh
  • Han G Brunner
  • Meredith Wilson
  • Laurence Faivre
  • Vera M Kalscheuer
  • Julien Thevenon
  • Asifa Akhtar
View graph of relations

The etiological spectrum of ultra-rare developmental disorders remains to be fully defined. Chromatin regulatory mechanisms maintain cellular identity and function, where misregulation may lead to developmental defects. Here, we report pathogenic variations in MSL3, which encodes a member of the chromatin-associated male-specific lethal (MSL) complex responsible for bulk histone H4 lysine 16 acetylation (H4K16ac) in flies and mammals. These variants cause an X-linked syndrome affecting both sexes. Clinical features of the syndrome include global developmental delay, progressive gait disturbance, and recognizable facial dysmorphism. MSL3 mutations affect MSL complex assembly and activity, accompanied by a pronounced loss of H4K16ac levels in vivo. Patient-derived cells display global transcriptome alterations of pathways involved in morphogenesis and cell migration. Finally, we use histone deacetylase inhibitors to rebalance acetylation levels, alleviating some of the molecular and cellular phenotypes of patient cells. Taken together, we characterize a syndrome that allowed us to decipher the developmental importance of MSL3 in humans.

Original languageEnglish
JournalNature Genetics
Volume50
Issue number10
Pages (from-to)1442-1451
Number of pages10
ISSN1061-4036
DOIs
Publication statusPublished - Oct 2018

ID: 56075925