Chronic inflammatory bowel disease as key manifestation of atypical ARTEMIS deficiency.
BACKGROUND
We describe a girl presenting at age 6 years with a history of chronic ulcerating intestinal inflammation since 9 months of age. She exhibited a severe, steroid-dependent clinical course of intestinal inflammation over several years in the absence of serious infections.


CONCLUSIONS
Immunodeficiency was first considered at 6 years of age due to chronic lymphopenia. Immunophenotyping revealed low B and T cell counts with few naïve T cells, a skewed TCR repertoire, and TCR gamma/delta T cell predominance, suggesting a defect of lymphocyte development. Genetic and functional analyses identified a hypomorphic mutation in the DCLRE1C (ARTEMIS) gene compromising V(D)J recombination efficiency, but allowing residual T and B cell development. Hematopoetic stem cell transplantation reconstituted the lymphocyte compartment and cured the inflammatory bowel disease.


CONCLUSIONS
This report illustrates that a genetic disorder of lymphocyte development can present with chronic inflammatory bowel disease as the dominant phenotype in the absence of severe infection susceptibility.
Rohr
Jan
J
Centre of Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
Pannicke
Ulrich
U
Döring
Michaela
M
Schmitt-Graeff
Annette
A
Wiech
Elisabeth
E
Busch
Andreas
A
Speckmann
Carsten
C
Müller
Ingo
I
Lang
Peter
P
Handgretinger
Rupert
R
Fisch
Paul
P
Schwarz
Klaus
K
Ehl
Stephan
S
D002460:Cell Line; D002648:Child; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D004720:Endonucleases; D005260:Female; D019672:Genes, T-Cell Receptor / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D008231:Lymphopenia; D038041:Lymphopoiesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014456:Ulcer
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases