RESUMEN
OBJECTIVE: Prader-Willi syndrome (PWS) is a genomic imprinting disorder predominantly caused by the absence of paternally expressed imprinted genes at chromosome 15q11.2-q13. The PCSK1 gene is vital for the processing of hypothalamic POMC to ACTH and α-MSH, leading to food intake suppression and increased energy expenditure. The aim of this study was to investigate whether our PWS patient had a defect in genes involved in the hypothalamic melanocortin-4 receptor (MC4R) pathway. PATIENTS AND METHODS: A 27-year-old Greek man with PWS presented to the Adult Endocrine Clinic with morbid obesity and hyperphagia. He also had obstructive sleep apnea, growth hormone deficiency, gonadal failure and metabolic disturbances. At 6 years of age, chromosomal testing confirmed PWS with a deletion in the q11q13 region of the long arm of paternal chromosome 15. RESULTS: At the age of 27 years, further genetic testing was conducted, and next generation sequencing revealed a PCSK1_pN221D_HET mutation which was confirmed by Sanger sequencing. CONCLUSIONS: Our findings suggest that different genetic abnormalities may be present in an individual with PWS and that patients with PWS may need to be investigated for PCSK1 mutations, as the finding may potentially offer a novel treatment perspective for them.
