Characterisation of complex chromosome 18p rearrangements in two syndromic patients with immunological deficits

There have been reports that a number of patients with a chromosome 18pter deletion have developed autoimmune disorders, including juvenile diabetes, rheumatoid arthritis, thyroiditis and Graves’ disease, and/or show little or no reduction in serum IgA levels. We describe two female patients bearing complex rearrangements involving chromosome 18p. Array-CGH and BAC FISH molecular cytogenetic analyses enabled the precise identification of the affected 18p region. One patient has a 2 Mb terminal deletion associated with a 9.2 Mb inverted duplication of the adjacent region; the other has a more extended 10.1 Mb terminal deletion associated with a 4.1 Mb quadruplication of the adjacent region and a 2.6 Mb duplication of the pericentromeric region. Both patients have dysmorphic features typical of 18p syndrome, such as growth retardation, epicanthal folds, a long philtrum and toe defects, and are also affected by immunological disorders. One has a form of immunological deficiency that takes the form of recurrent pulmonary infections and low IgA levels; the other has an autoimmune form of juvenile rheumatoid arthritis. Relating the refined molecular cytogenetic characterisation of these 18p chromosomal rearrangements to the patients’ specific clinical characteristics can improve our understanding of the role of the 18p region in immune responses.