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

Abstract

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.

• Authors: Johanne Le Beyec, Christine Cugnet-Anceau, Dominique Pépin, Rohia Alili, Aurelie Cotillard, Jean-Marc Lacorte, Arnaud Basdevant, Martine Laville, Karine Clément
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 98 Issue 2 Pg. E397-402 (Feb 2013) ISSN: 1945-7197 [Electronic] United States
• PMID: 23275530 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Leptin

Topics

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