Seven Novel Deleterious LEPR Mutations Found in Early-Onset Obesity: a ΔExon6–8 Shared by Subjects From Reunion Island, France, Suggests a Founder Effect
| Autor: | Martine Laville, Marc Nicolino, Hélène Huvenne, Erwan Jeannic, Amélie Viard, Béatrice Dubern, Séverine Ledoux, Patrick Tounian, Johanne Le Beyec, Jean-Marc Lacorte, Marie-Laure Frelut, Christine Poitou, Rohia Alili, Karine Clément, Patricia Pigeon Kherchiche, Dominique Pepin |
|---|---|
| Přispěvatelé: | Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Founder Effect Obesity/*genetics Genotype [SDV]Life Sciences [q-bio] Endocrinology Diabetes and Metabolism Clinical Biochemistry 030209 endocrinology & metabolism Context (language use) Biology medicine.disease_cause Biochemistry 03 medical and health sciences Exon 0302 clinical medicine Endocrinology Receptors medicine Humans Obesity 030304 developmental biology 2. Zero hunger Genetics Body Composition/genetics 0303 health sciences Mutation Leptin receptor Biochemistry (medical) Exons Heterozygote advantage Middle Aged medicine.disease 3. Good health Phenotype Body Composition Receptors Leptin Female France Leptin/*genetics Founder effect |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2015, 100 (5), pp.E757-66. ⟨10.1210/jc.2015-1036⟩ |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2015-1036 |
| Popis: | International audience; CONTEXT: Infrequent mutations have been reported in the leptin receptor (LEPR) gene in humans with morbid obesity and endocrine disorders. However LEPR mutations are rarely examined in large populations from different ethnicities in a given country. OBJECTIVE: We estimated the prevalence of LEPR mutations in French patients with severe obesity and evaluated mutated patients' phenotype. DESIGN AND PATIENTS: We sequenced the LEPR gene in 535 morbidly obese French participants. We conducted clinical investigations to determine whether individuals with a novel shared mutation display particular characteristics relative to obesity history, body composition, hormonal functions, and the outcome of bariatric surgery. RESULTS: We identified 12 patients with a novel LEPR mutation (p.C604G, p.L786P, p.H800_N831del, p.Y422H, p.T711NfsX18, p.535-1G\textgreaterA, p.P166CfsX7). Six unrelated subjects were carriers of the p.P166CfsX7 mutation leading to deletion overlapping exons 6 to 8. All subjects originated from Reunion Island (France). Their clinical features (severe early-onset obesity, food impulsivity, and hypogonadotropic hypogonadism) did not differ from other new LEPR mutation carriers. Results concerning weight loss surgery were inconsistent in homozygous LEPR mutation carriers. Heterozygous LEPR mutation carriers exhibited variable severity of obesity and no endocrine abnormality. CONCLUSION: Among seven newly discovered LEPR mutations in this French obese population, we identified a LEPR frameshift mutation shared by six subjects from Reunion Island. This observation suggests a founder effect in this Indian Ocean island with high prevalence of obesity and supports a recommendation for systematic screening for this mutation in morbidly obese subjects in this population. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|