Homozygous Leptin Receptor Mutation Due to Uniparental Disomy of Chromosome 1: Response to Bariatric Surgery

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 2; pp. E397 - E402
• Main Authors: Le Beyec, Johanne, Cugnet-Anceau, Christine, Pépin, Dominique, Alili, Rohia, Cotillard, Aurelie, Lacorte, Jean-Marc, Basdevant, Arnaud, Laville, Martine, Clément, Karine
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.02.2013; Copyright by The Endocrine Society
• Subjects: Adolescent; Adult; Amino acid sequence; Bariatric Surgery; Body weight loss; Chromosome 1; Chromosomes; Chromosomes, Human, Pair 1; Gastrointestinal surgery; Genetic analysis; Homozygote; Humans; Hyperphagia; Hyperphagia - genetics; Hyperphagia - surgery; Hypogonadism; Hypothalamus; Male; Nonsense mutation; Obesity; Obesity, Morbid - genetics; Obesity, Morbid - surgery; Patients; Puberty; Receptors, Leptin - genetics; Stop codon; Surgery; Treatment Outcome; Uniparental Disomy; Weight control
• DOI: 10.1210/jc.2012-2779
• ISSN: 0021-972X; 1945-7197

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.