title: Homozygous leptin receptor mutation due to uniparental disomy of chromosome 1: response to bariatric surgery.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institut National de la Santéet de la Recherche Médicale (INSERM), Unité (U)872, Team 7, Nutriomique, Universite´ Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, 75006 Paris, France.
authors.forename: Johanne
authors.initials: J
authors.lastname: Le Beyec
authors.forename: Christine
authors.initials: C
authors.lastname: Cugnet-Anceau
authors.forename: Dominique
authors.initials: D
authors.lastname: Pépin
authors.forename: Rohia
authors.initials: R
authors.lastname: Alili
authors.forename: Aurelie
authors.initials: A
authors.lastname: Cotillard
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lacorte
authors.forename: Arnaud
authors.initials: A
authors.lastname: Basdevant
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
mesh_terms: D000293:Adolescent; D000328:Adult; D050110:Bariatric Surgery; D002878:Chromosomes, Human, Pair 1; D006720:Homozygote; D006801:Humans; D006963:Hyperphagia / Q000235:genetics / Q000601:surgery; D008297:Male; D009767:Obesity, Morbid / Q000235:genetics* / Q000601:surgery; D054411:Receptors, Leptin / Q000235:genetics*; D016896:Treatment Outcome; D024182:Uniparental Disomy
chemical_list: D054411:Receptors, Leptin