Inflammatory Bowel Disease 28, Autosomal Recessive

A number sign (#) is used with this entry because of evidence that inflammatory bowel disease-28 (IBD28) is caused by homozygous or compound heterozygous mutation in the IL10RA gene (146933) on chromosome 11q23.

Another form of early-onset inflammatory bowel disease, IBD25 (612567), is caused by mutation in the IL10RB gene (123889) encoding the IL10R2 protein, which, together with the IL10R1 protein encoded by IL10RA, forms the heterotetrameric IL10 (124092) receptor.

For a general description and discussion of genetic heterogeneity of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis, see IBD1 (266600).

Clinical Features

Glocker et al. (2009) reported a girl from a consanguineous Lebanese family who presented in the first year of life with severe enterocolitis associated with enteric fistulas, perianal abscesses, and chronic folliculitis, consistent with a diagnosis of Crohn disease. She required multiple surgical interventions, including colectomy and ileostomy.

Begue et al. (2011) studied a French boy who had onset of perianal lesions and pancolitis with granulomas at 1 month of age. The first signs of small bowel inflammation appeared at 9 years of age, with subsequent continuous aggravation; he also developed episodes of cutaneous folliculitis as well as bronchial infections. The patient's hematopoietic cells showed a lack of response to IL10 (124092).

Mao et al. (2012) described a 3.5-year-old Chinese boy who in the second week of life presented with fever and oral ulceration, then bloody loose stools. At 3 months of age, he had perianal ulceration, and at 6 months he continued to have bloody loose stools and perianal granulomata, as well as intermittent pyoderma. Colonoscopy revealed colitis involving the rectum, sigmoid colon, and descending colon, and biopsy showed nonspecific inflammation.

Mapping

In a consanguineous Lebanese family with early-onset severe enterocolitis, Glocker et al. (2009) performed genomewide homozygosity mapping and identified a region of interest on chromosome 11q between rs4938219 and rs3829261.

Molecular Genetics

In a consanguineous Lebanese family with early-onset severe enterocolitis, Glocker et al. (2009) analyzed the IL10RA gene and identified homozygosity for a missense mutation in the proband (146933.0001). Unaffected family members were heterozygous for the mutation, which was not found in 100 Arabic controls or 30 Iranian controls. Analysis of IL10RA in 6 additional patients with onset of severe colitis in the first year of life revealed a homozygous missense mutation in a German patient (146933.0002); no mutations were found in 32 children with IBD who had onset of symptoms at more than 12 months of age.

In a French boy who had onset of perianal lesions and pancolitis with granulomas at 1 month of age, in whom hematopoietic cells showed a lack of response to IL10, Begue et al. (2011) identified homozygosity for a missense mutation in the IL10RA gene (146933.0003). His unaffected parents and brother were heterozygous for the mutation.

In a 3.5-year-old boy with neonatal-onset Crohn disease, Mao et al. (2012) performed whole-exome sequencing followed by filtering and identified compound heterozygosity for missense mutations in the IL10RA gene (146933.0004 and 146933.0005). Sanger sequencing confirmed the mutations and showed that his unaffected parents were each heterozygous for 1 of the mutations.