To the Editor:

We congratulate Glocker et al1 for linking human interleukin (IL)-10R mutations (as found in immigrant families from the Middle East) and infancy-onset inflammatory bowel disease (IBD), a hypothesis we have followed for some years.

When searching for mutations in IL-10RA we had identified two common variants2 (including S138G, which is just 18 amino acids downstream of the G141R mutation1 and inconsistently linked to colitis3) but also a truncated IL-10RA allele that was missing a 179-basepair fragment (Fig. 1). Surprisingly this EX3del mutation was from a heterozygote Austrian Semite who did not display a disease phenotype. The mutation was traced to the father and the uncle who had emigrated from Iraq. We therefore screened various IBD cohorts from Austria, Israel, Lebanon, Jordan, and Morocco for this specific mutation but were unable to identify a homozygous individual in 1100 adult-onset and 120 pediatric cases (two of whom were diagnosed within the first year of life).

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Figure 1. Genomic localization of the IL-10RA EX3del mutation. An A-to-G point mutation at the splice acceptor site of exon 3 was identified at position 3230 (g. 3230A>G) leading to the loss of a 179-bp fragment and a frameshift. The predicted 94-aa protein lacks both transmembrane and intracellular domains. The individual was heterozygote for this mutation. SP, signaling peptide; ECD, extracellular domain; TMD, transmembrane domain; ICD, intracellular domain.

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From the report by Glocker et al we know that IL-10R deficiency is not embryonically lethal. Based on our observation, it is plausible that several truncating IL-10R mutations exist in IL-10Rs specifically in Semite descendants who will require advanced medical attention early in life.


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  • 1
    Glocker EO, Kotlarz D, Boztug K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009; 361: 20332045.
  • 2
    Gasche C, Grundtner P, Zwirn P, et al. Novel variants of the IL-10 receptor 1 affect inhibition of monocyte TNF-alpha production. J Immunol. 2003; 170: 55785582.
  • 3
    Grundtner P, Gruber S, Murray SS, et al. The IL-10R1 S138G loss-of-function allele and ulcerative colitis. Genes Immun. 2009; 10: 8492.

Christoph Gasche MD* †, Walter Reinisch MD*, Wolf-Dietrich Huber MD‡, Esther Leshinsky-Silver PhD§, Arie Levine MD¶, Heitham Abdul-Baki MD**, Ala I. Sharara MD**, Yousef Ajlouni MD††, Abdelaziz Sefiani PhD‡‡, * Department of Medicine 3, Divisions of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria, † Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Medical University of Vienna Vienna, Austria, ‡ Department Pediatrics, Medical University of Vienna, Vienna, Austria, § Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Israel, ¶ Pediatric Gastroenterology Unit, Wolfson Medical Center, Holon, Israel, ** Division of Gastroenterology and Hepatology, American University of Beirut Medical Center, Beirut, Lebanon, †† Deparment of Internal Medicine, King Hussein Medical Center, Amman, Jordan, ‡‡ Department Medical Genetics, National Institute of Health Rabat, Morocco.