Investigation of a patient with a partial trisomy 16q including the fat mass and obesity associated gene (FTO): fine mapping and FTO gene expression study.

A female patient with a partial trisomy 16q was described previously. Her clinical characteristics included obesity, severe anisomastia, moderate to severe mental retardation, attention deficit hyperactivity disorder, dysmorphic facies, and contractions of the small joints. In this article, we describe a more detailed analysis of the genetic anomaly in this patient. We were particularly interested in the involvement of the fat mass and obesity associated gene (FTO) in her duplication. Single nucleotide polymorphisms in FTO have been associated with obesity. The breakpoints of the duplication were precisely mapped using high-resolution oligonucleotide array comparative genomic hybridization (CGH). We found that the duplication spans 11.45 Mb on 16q11.2 to 16q13 and it includes FTO. The increased copy number of FTO was confirmed with a qPCR on genomic DNA of the patient. We investigated the influence of the increased FTO copy number on FTO gene expression in immortalized lymphocytes from the patient using qPCR. No evidence of increased FTO expression was detected in the patient's lymphocytes. We discuss these findings and we review clinical findings in patients with overlapping 16q duplications to determine the relationship between increased FTO copy number and obesity. Our review suggests that duplication of the FTO gene does not necessarily result in obesity.