DISCUSSION Here we report on the fifth case of chromosome 6q deletion in association with a Prader-Willi-like phenotype. A review of five patients with an interstitial chromosome 6q deletion and a Prader-Willi-like phenotype showed that they all shared the following features with Prader-Willi syndrome patients: obesity, hypotonia, short extremities, and developmental delay. 2–5 However, there are also distinct differences. For example, excessive appetite was seen in only two patients and cardiac (bicuspid aortic valve, aortic stenosis, right branch block) as well as neurological abnormalities (polygyria, leucomalacia, seizures, hearing loss, Arnold-Chiari malformation) were found in 2/5 and 3/5 patients, respectively. These differences are summarised in table 1.

Interestingly, four out of five patients described have a 6q16. 2 deletion (fig 3). This suggests that the 6q16. 2 subband could be regarded as a region of interest for obesity related genes. In addition, a balanced translocation between chromosomes 1p22. 1 and 6q16. 2 has been reported in a patient with profound obesity. 6 The authors cloned and sequenced both translocation breakpoints. While the translocation did not appear to affect any transcription unit on 1p22. 1, it disrupted the SIM1 gene on 6q16. 2. They hypothesised that haploinsufficiency of SIM1, possibly acting upstream or downstream of the melanocortin 4 receptor in the paraventricular nuclei of the hypothalamus, could be responsible for obesity in their subject. Indeed, it has been shown in the mouse that the Sim1 gene is expressed in the central nervous system where it has