Homozygous leptin receptor mutation due to uniparental disomy of chromosome 1: response to bariatric surgery

J Clin Endocrinol Metab. 2013 Feb;98(2):E397-402. doi: 10.1210/jc.2012-2779. Epub 2012 Dec 28.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bariatric Surgery*
  • Chromosomes, Human, Pair 1*
  • Homozygote*
  • Humans
  • Hyperphagia / genetics
  • Hyperphagia / surgery
  • Male
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / surgery
  • Receptors, Leptin / genetics*
  • Treatment Outcome
  • Uniparental Disomy*


  • Receptors, Leptin