Our research work aims to elucidate the transcriptional regulatory mechanism playing a cardinal role in human development using rare developmental syndromes as a model.

About Research

To elucidate the transcriptional regulatory mechanism though rare disease research

There are many rare multiple malformation syndromes associated with birth defects, and these syndromes can provide us with valuable opportunities to understand the pathogenic mechanisms of birth defects, since the molecular mechanisms of isolated birth defects remain largely unknown. Thanks to the introduction of advance genetic testing methodology, such as exome sequencing, it has become easier to pinpoint a causative genetic alteration leading to a multiple malformation syndrome. However, the molecular mechanisms by which these mutations lead to multiple malformations remain largely unknown. Our laboratory aim to elucidate the transcriptional regulatory mechanism using rare pediatric developmental disorders such as CHOPS syndrome and ARCN1-related syndrome as a model.


  1. Izumi K., Nakato R., Zhang Z., Edmondson AC., Noon S., Dulik MC., Rajagopalan R., Venditti CP., Gripp K., Samanich J., Zackai EH., Deardorff MA., Clark D., Allen JL., Dorsett D., Misulovin Z., Komata M., Bando M., Kaur M., Katou Y., Shirahige K., Krantz ID. (2015) “Germline Gain-of-Function Mutations in AFF4 Cause a Developmental Syndrome Functionally Linking the Super Elongation Complex and Cohesin” Nat Genet. 47(4):338-44.
  2. Izumi K. (2016) “Disorders of Transcriptional Regulation: An Emerging Category of Multiple Malformation Syndromes” Mol Syndromol. 7(5):262-273.
  3. Izumi K, Brett M, Nishi E, Drunat S, Tan ES, Fujiki K, Lebon S, Cham B, Masuda K, Arakawa M, Jacquinet A, Yamazumi Y, Chen ST, Verloes A, Okada Y, Katou Y, Nakamura T, Akiyama T, Gressens P, Foo R, Passemard S, Tan EC, El Ghouzzi V, Shirahige K. (2016) “ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-mediated Transport Defects” Am J Hum Genet. 99(2):451-9.
  4. Iwata-Otsubo A, Ritter AL, Weckselbatt B, Ryan NR, Burgess D, Conlin LK, Izumi K. (2018) “DOCK3-related neurodevelopmental syndrome: Biallelic Intragenic Deletion of DOCK3 in a Boy with Developmental Delay and Hypotonia” Am J Med Genet. 176 (1) 241-245.
  5. Ritter AL, Mcdougall C, Skraban C, Medne L, Bedoukian EC, Asher SB, Balciuniene J, Campbell CD, Baker SW, Denenberg EH, Mazzola S, Fiordaliso SK, Krantz ID, Kaplan P, Ierardi-Curto L, Santani AB, Zackai EH, Izumi K. (2018) “Variable Clinical Manifestations of Xia-Gibbs syndrome: Findings of Consecutively Identified Cases at a Single Children’s Hospital” Am J Med Genet. 176(9):1890-1896.
Kosuke Izumi
Visiting Associate Professor