Journal of Clinical Immunology

, Volume 39, Issue 6, pp 616–619 | Cite as

Novel Exonic Deletions in TTC7A in a Newborn with Multiple Intestinal Atresia and Combined Immunodeficiency

  • Jessica R. Saunders
  • Anna Lehman
  • Stuart E. Turvey
  • Jie Pan
  • Evica Rajcan-Separovic
  • Aleixo M. Muise
  • Jonathan W. BushEmail author
Letter to Editor

To the Editor:

Hereditary multiple intestinal atresia and combined immunodeficiency (MIA-CID, also referred to as gastrointestinal defects and immunodeficiency syndrome (GIDID); OMIM: 243150; reviewed in Jardine and Muise 2019 [1]) is an extremely rare and typically lethal disorder. This condition is characterized by multiple intestinal obstructions with atretic sites occurring throughout the small and large intestines. In addition, the gastrointestinal manifestations can include very early onset inflammatory bowel disease (VEOIBD). These intestinal features are associated with a spectrum of immunodeficiency, ranging from mild lymphocytopenia to severe combined immunodeficiency. Total parental nutrition (TPN) dependence and recurrent bouts of sepsis caused largely by intestinal bacteria make the prognosis very poor [2], with very few children surviving beyond the first years of life. The genetic basis of this condition has recently been linked to autosomal recessive mutations in TTC7A...


Multiple intestinal atresia combined immunodeficiency TTC7A VEOIBD 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Jardine S, Dhingani N, Muise AM. TTC7A: steward of intestinal health. Cell Mol Gastroenterol Hepatol 2018:Google Scholar
  2. 2.
    Agarwal NS, Northrop L, Anyane-Yeboa K, Aggarwal VS, Nagy PL, Demirdag YY. Tetratricopeptide repeat domain 7A (TTC7A) mutation in a newborn with multiple intestinal atresia and combined immunodeficiency. J Clin Immunol. 2014;34(6):607–10.CrossRefGoogle Scholar
  3. 3.
    Bigorgne AE, Farin HF, Lemoine R, Mahlaoui N, Lambert N, Gil M, et al. TTC7A mutations disrupt intestinal epithelial apicobasal polarity. J Clin Invest. 2014;124(1):328–37.CrossRefGoogle Scholar
  4. 4.
    Avitzur Y, Guo C, Mastropaolo LA, Bahrami E, Chen H, Zhao Z, et al. Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease. Gastroenterology. 2014;146(4):1028–39.CrossRefGoogle Scholar
  5. 5.
    Chen R, Giliani S, Lanzi G, Mias GI, Lonardi S, Dobbs K, et al. Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias. J Allergy Clin Immunol. 2013;132(3):656–664.e17.CrossRefGoogle Scholar
  6. 6.
    Samuels ME, Majewski J, Alirezaie N, Fernandez I, Casals F, Patey N, et al. Exome sequencing identifies mutations in the gene TTC7A in French-Canadian cases with hereditary multiple intestinal atresia. J Med Genet. 2013;50(5):324–9.CrossRefGoogle Scholar
  7. 7.
    Yang W, Lee PPW, Thong MK, Ramanujam TM, Shanmugam A, Koh MT, et al. Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency. Clin Genet. 2015;88:542–9.CrossRefGoogle Scholar
  8. 8.
    Kammermeier J, Lucchini G, Pai SY, Worth A, Rampling D, Amrolia P, et al. Stem cell transplantation for tetratricopeptide repeat domain 7A deficiency: long-term follow up. Blood. 2016;128(9):1306–8.CrossRefGoogle Scholar
  9. 9.
    Leclerc-Mercier S, Lemoine R, Bigorgne AE, Sepulveda F, Leveau C, Fischer A, et al. Ichthyosis as the dermatological phenotype associated with TTC7A mutations. Br J Dermatol. 2016;176:1061–4.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineThe University of British ColumbiaVancouverCanada
  2. 2.Department of Medical Genetics, British Columbia Children’s and Women’s HospitalThe University of British ColumbiaVancouverCanada
  3. 3.Department of Pediatrics, British Columbia Children’s HospitalThe University of British ColumbiaVancouverCanada
  4. 4.SickKids Inflammatory Bowel Disease Center and Cell Biology Program Research InstituteThe Hospital for Sick ChildrenTorontoCanada
  5. 5.Department of Pathology and Laboratory Medicine, British Columbia Children’s and Women’s HospitalThe University of British ColumbiaVancouverCanada
  6. 6.Departments of Pediatrics, Institute of Medical Science and BiochemistryThe University of TorontoTorontoCanada

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