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.
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 obesepatient 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: Alejandro Campos; Lizeth Cifuentes; Anas Hashem; Bradley Busebee; Maria D Hurtado-Andrade; Maria L Ricardo-Silgado; Alison McRae; Alan De la Rosa; Fauzi Feris; Joshua T Bublitz; Donald Hensrud; Michael Camilleri; Todd A Kellogg; Jeanette E Eckel-Passow; Janet Olson; Andres Acosta Journal: Obes Surg Date: 2022-06-03 Impact factor: 3.479
Authors: Niels Vos; Sabrina M Oussaada; Mellody I Cooiman; Lotte Kleinendorst; Kasper W Ter Horst; Eric J Hazebroek; Johannes A Romijn; Mireille J Serlie; Marcel M A M Mannens; Mieke M van Haelst Journal: Curr Diab Rep Date: 2020-07-30 Impact factor: 4.810
Authors: Martin Wabitsch; Sadaf Farooqi; Christa E Flück; Natasa Bratina; Usha G Mallya; Murray Stewart; Jill Garrison; Erica van den Akker; Peter Kühnen Journal: J Endocr Soc Date: 2022-04-15