Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin Receptor

• Published in: The New England journal of medicine Vol. 356; no. 3; pp. 237 - 247
• Main Authors: Farooqi, I. Sadaf, Wangensteen, Teresia, Collins, Stephan, Kimber, Wendy, Matarese, Giuseppe, Keogh, Julia M, Lank, Emma, Bottomley, Bill, Lopez-Fernandez, Judith, Ferraz-Amaro, Ivan, Dattani, Mehul T, Ercan, Oya, Myhre, Anne Grethe, Retterstol, Lars, Stanhope, Richard, Edge, Julie A, McKenzie, Sheila, Lessan, Nader, Ghodsi, Maryam, De Rosa, Veronica, Perna, Francesco, Fontana, Silvia, Barroso, Inês, Undlien, Dag E, O'Rahilly, Stephen
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 18.01.2007
• Subjects: Adult; Age; Age of Onset; Basal Metabolism; Biological and medical sciences; Body Composition; Child; Diagnosis, Differential; Female; General aspects; Genes; Genetic counseling; Genotype; Humans; Hyperphagia - blood; Hyperphagia - complications; Hyperphagia - genetics; Hypogonadism - blood; Hypogonadism - complications; Hypogonadism - genetics; Immunologic Deficiency Syndromes - blood; Immunologic Deficiency Syndromes - complications; Immunologic Deficiency Syndromes - genetics; Leptin - blood; Lymphocyte Count; Male; Medical sciences; Metabolism, Inborn Errors - blood; Metabolism, Inborn Errors - diagnosis; Metabolism, Inborn Errors - genetics; Mutation; Obesity; Obesity - blood; Obesity - complications; Obesity - genetics; Original; Pedigree; Phenotype; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Receptors, Leptin; Studies; Medicine; Symptomatology; Congenital; Deficiency; Leptin; Genetics; Biological receptor
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa063988

Of 300 persons selected for early-onset obesity, hyperphagia, and consanguineous parentage, 8 had mutations in the leptin-receptor gene ( LEPR ). Biochemical and clinical analyses of the affected subjects suggest that the assay of serum leptin levels is not an appropriate screening tool for LEPR mutations and that the LEPR protein product may not be the only leptin receptor in humans. Biochemical and clinical analyses suggest that the assay of serum leptin levels is not an appropriate screening tool for LEPR mutations and that the LEPR protein product may not be the only leptin receptor in humans. The assessment of patients with severe early-onset obesity conventionally includes screening for potentially treatable neurologic and endocrine conditions and identifying known genetic conditions so that appropriate genetic counseling and, in some cases, treatment can be instituted. 1 Classically, patients with genetic obesity syndromes have been identified in childhood as a result of associated mental retardation and developmental abnormalities. 2 However, several monogenic disorders have been identified in which obesity itself is the predominant presenting feature. These disorders result from disruption of the hypothalamic leptin–melanocortin signaling pathway. 3 – 8 Twelve subjects with congenital leptin deficiency due to loss-of-function mutations in the gene encoding leptin . . .