Abstract for presentation at 11th International Congress of Human Genetics

Three different classes of 6q deletions with shared phenotypic features have been described (Hopkins et al. 1997). Rare cases with microdeletions indicate that within deletion group B spanning from 6q15 to 6q25 a distinct subgroup of patients with PWLP may result from hemizygosity of a short chromosome segment covered by bands 6q16 and 6q21 including also the SIM1 gene (Faivre et al. 2005). We report about a 16-year-old girl with adipositas (BMI 30), severe mental retardation and other major features of PWLP. Basedow´s disease and acanthosis nigricans were seen in addition to macrocephalus, dental anomalies, uvula bifida and kyphosis. Cytogenetic and microsatellite analysis in the family revealed a de novo paternal microdeletion including SIM1 at 6q16.3. Our study confirms the assumption that 6q16-q21 microdeletions including the SIM1 gene are associated with obesity and PWLP. Recently it has been assumed that hemizyosity and/or functional loss of SIM1 is associated with hyperphagic obesity via a disturbed regulation of MC4R expression in the paraventricular nuclei of hypothalamus (Holden et al. 2005). Basedow´s disease and acanthosis nigricans have not been reported so far in the context of deletions of that chromosome segment. These additional clinical features of our patient would indicate that hemizygosity for that 6q segment including SIM1 has additional neuroendocrinological effects, e.g. such as on the level of TRH and MSH.