Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor
| Autor: | Wendy Kimber, Stephen O'Rahilly, Anne Grethe Myhre, Oya Ercan, J. A. Edge, Veronica De Rosa, Silvia Fontana, Teresia Wangensteen, Giuseppe Matarese, Dag E. Undlien, Stephan C. Collins, Sheila A. McKenzie, Francesco Perna, Nader Lessan, Maryam Ghodsi, Bill Bottomley, Iván Ferraz-Amaro, Emma Lank, Inês Barroso, Mehul T. Dattani, Judith López-Fernández, I. Sadaf Farooqi, Richard Stanhope, Lars Retterstøl, Julia M. Keogh |
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| Přispěvatelé: | Farooqi, I, Wangensteen, T, Collins, S, Kimber, W, Matarese, G, Keogh, Jm, Lank, E, Bottomley, B, LOPEZ FERNANDEZ, J, FERRAZ AMARO, I, Dattani, Mt, Ercan, O, Myhre, Ag, Retterstol, L, Stanhope, R, Edge, Ja, Mckenzie, S, Lessan, N, Ghodsi, M, DE ROSA, V, Perna, Francesco, Fontana, S, Barroso, I, Undlien, De, O'Rahilly, S. |
| Rok vydání: | 2007 |
| Předmět: |
Delayed puberty
Adult Leptin Male medicine.medical_specialty Genotype Receptors Cell Surface Hyperphagia Compound heterozygosity Article Diagnosis Differential Hypogonadotropic hypogonadism Internal medicine medicine Missense mutation Humans Lymphocyte Count Obesity Age of Onset Child Leptin receptor business.industry Hypogonadism digestive oral and skin physiology Immunologic Deficiency Syndromes General Medicine medicine.disease Pedigree Endocrinology Phenotype Mutation Body Composition Receptors Leptin Female Basal Metabolism medicine.symptom Age of onset business hormones hormone substitutes and hormone antagonists Metabolism Inborn Errors |
| Zdroj: | New England journal of medicine (Online) (2007). info:cnr-pdr/source/autori:Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, Lank E, Bottomley B, Lopez-Fernandez J, Ferraz-Amaro I, Dattani MT, Ercan O, Myhre AG, Retterstol L, Stanhope R, Edge JA, McKenzie S, Lessan N, Ghodsi M, De Rosa V, Perna F, Fontana S, Barroso I, Undlien DE, O'Rahilly S./titolo:Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor/doi:/rivista:New England journal of medicine (Online)/anno:2007/pagina_da:/pagina_a:/intervallo_pagine:/volume New England journal of medicine (Online) 356 (2007): 237–247. doi:10.1056/NEJMoa063988 info:cnr-pdr/source/autori:Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, Lank E, Bottomley B, Lopez-Fernandez J, Ferraz-Amaro I, Dattani MT, Ercan O, Myhre AG, Retterstol L, Stanhope R, Edge JA, McKenzie S, Lessan N, Ghodsi M, De Rosa V, Perna F, Fontana S,/titolo:Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor./doi:10.1056%2FNEJMoa063988/rivista:New England journal of medicine (Online)/anno:2007/pagina_da:237/pagina_a:247/intervallo_pagine:237–247/volume:356 |
| Popis: | BACKGROUND: A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined. METHODS: We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives. RESULTS: Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations -- 7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency. CONCLUSIONS: The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism |
| Databáze: | OpenAIRE |
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