1. Congenital Leptin Deficiency and Leptin Gene Missense Mutation Found in Two Colombian Sisters with Severe Obesity
- Author
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Monica Alvarez-Jaramillo, Luis G. Celis-Regalado, Carlos Martín Restrepo, Alexandra Arias-Serrano, Angelica M. Garcia-Ordoñez, Shelley A. Cole, Mauricio Arcos-Burgos, Jack W. Kent, Claudio A. Mastronardi, Edna J. Nava-González, Maria E. Yupanqui-Velazco, Carolina Torres-Forero, Julio Licinio, Ernesto Rodríguez-Ayala, Aida P. Giraldo-Peña, Raul A. Bastarrachea, Esteban Medina-Méndez, and Hernan Yupanqui-Lozno
- Subjects
Luteinizing hormone ,Leptin ,Hirsutism ,Thyrotropin ,Nail hypoplasia ,Dna sequence ,Gene ,Morbid obesity ,Consanguinity ,0302 clinical medicine ,Insulin ,Sleeve gastrectomy ,Child ,High density lipoprotein cholesterol ,Mutation ,Leptin Deficiency ,Estradiol ,digestive, oral, and skin physiology ,Genetic disorder ,LEP gene ,Metformin ,Obesity, Morbid ,Pedigree ,Colombian ,Human ,Pcsk1 gene ,medicine.medical_specialty ,Novel mutation ,Clinical article ,Mc4r gene ,Colombia ,Triacylglycerol ,Congenital leptin deficiency ,Article ,03 medical and health sciences ,consanguinity ,Pomc gene ,Case report ,Genetics ,Humans ,Gene deletion ,Pparg gene ,medicine.disease ,Knee pain ,Extreme obesity ,Obesity ,Prolactin ,Strabismus ,Glucose ,030104 developmental biology ,Endocrinology ,Acne ,Leptin deficiency ,School child ,0301 basic medicine ,Enzyme linked immunosorbent assay ,Walking ,medicine.disease_cause ,Homozygosity ,congenital leptin deficiency ,Exon ,Hemoglobin a1c ,Lep gene ,Missense mutation ,Protein blood level ,Childhood obesity ,extreme obesity ,Amenorrhea ,Genetics (clinical) ,Hypertriglyceridemia ,Point mutation ,Fat mass ,Body weight gain ,Exons ,Body mass ,Telangiectasia ,Female ,hormones, hormone substitutes, and hormone antagonists ,Adult ,Lepr gene ,Adolescent ,lcsh:QH426-470 ,Colombian sisters ,Mutation, Missense ,030209 endocrinology & metabolism ,Biology ,Physical examination ,Clinodactyly ,Gene insertion ,Next generation sequencing ,Internal medicine ,medicine ,Disease severity ,Dietary intake ,Siblings ,Genomic dna ,Insulin resistance ,Follitropin ,lcsh:Genetics ,Young adult ,Clinical feature ,Preschool child ,Gemfibrozil ,novel mutation - Abstract
Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. Methods: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. Results: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G>, T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. Conclusions: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America.
- Published
- 2019
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