Veronica Silva Vilela, MD, Nilson Ramirez de Jesus, MD and Roger Abramino Levy, MD, PhD
by Amir Karban, MD, Rami Eliakim, MD and Steven R. Brant, MD
The etiology of inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided limited insight into disease pathogenesis. There is ample evidence that these diseases are in part the result of genetic predisposition. The early search for candidate genes focused on genes involved in the regulation of immune function.
Recent genome wide searches reported several susceptibility loci for Crohn’s disease and ulcerative colitis. The recent identification of the IBD1 gene (NOD2) with mutations that are associated with susceptibility to Crohn’s disease will have a major impact on the understanding of the genetics of this disease.
Hannah Tamary, MD, Raanan Bar-Yam, BSc, Michal Zemach, MD, Orly Dgany, PhD, Lea Shalmon, MSc and Isaac Yaniv, MD
Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.
Misha Witz, MD, Jonathan M. Lehmann, MB, BChir, Ali Shnaker, MD, Itamar Pomeranz, MD,George Leichtman, MD and Benthly Novis, MD, FRCP
Ashraf Hamdan, MD, Dania Hirsch, MD, Pnina Green, MD, PhD, Avivit Neumann, Tamara Drozd and Yair Molad, MD
Gadi Fishman, MD, Shaul Dollberg, MD, Liat Ben-Sira, MD and Ari DeRowe, MD
Craig Bjinderman, MA, Oren Lapid, MD and Gad Shaked, MD
Bernard Belhassen, MD and Aharon Glick, MD
Arie Shifman, DMD, Shmuel Orenbuch, MA and Mel Rosenberg, PhD