Homozygous Leptin Receptor Mutation Due to Uniparental Disomy of Chromosome 1: Response to Bariatric Surgery.
Le Beyec, Johanne; Cugnet-Anceau, Christine; Pepin, Dominique; Alili, Rohia; Cotillard, Aurelie; Lacorte, Jean-Marc; Basdevant, Arnaud; Laville, Martine; Clement, Karine
[Report]
Journal of Clinical Endocrinology & Metabolism.
98(2):E397-E402, February 2013.
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Context: Severe early-onset obesity with major hyperphagia associated with hypogonadotropic hypogonadism is recognized as the main clinical presentation of leptin (LEP) or LEP receptor (LEPR) gene complete deficiency. In a few reported cases, homozygous mutations have been found in patients from consanguineous families. Care of LEPR-deficient patients is complicated because they cannot benefit from LEP treatment. Furthermore, gastric surgery may not be recommended in such genetic hypothalamic obesity.
Objective: We investigated in a morbidly obese patient the genetic origin of his obesity and evaluated the benefit of bariatric surgery in this case.
Subject and Methods: The patient exhibited severe early-onset obesity with hyperphagia and delayed puberty in a nonobese family. He had clinical and hormonal follow-up from 3 to 26 years of age. Gastroplasty procedures were undertaken when he was 16 and 18 years old. LEPR genetic analysis of the patient and his relatives was performed.
Results: A new homozygous LEPR sequence frameshift, predicted to generate a truncated protein from a premature stop codon in exon 14, was identified in the proband inherited from two paternal copies of chromosome 1 (isodisomy). Vertical ring gastroplasty was sufficient to induce and maintain a 40-kg weight loss into adulthood.
Conclusion: We described the first case of a patient with chromosome 1 uniparental isodisomy revealed by molecular analysis of LEPR. In this case, gastroplasty may be partially effective for weight control as illustrated.
Copyright (C) 2013 by The Endocrine Society