Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity
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 phenom...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2019
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/24144
- Acceso en línea:
- https://doi.org/10.3390/genes10050342
https://repository.urosario.edu.co/handle/10336/24144
- Palabra clave:
- Estradiol
Follitropin
Gemfibrozil
Genomic dna
Glucose
Hemoglobin a1c
High density lipoprotein cholesterol
Insulin
Leptin
Luteinizing hormone
Metformin
Prolactin
Thyrotropin
Triacylglycerol
Acne
Adolescent
Adult
Amenorrhea
Article
Body mass
Body weight gain
Case report
Child
Childhood obesity
Clinical article
Clinical feature
Clinodactyly
Colombian
Consanguinity
Dietary intake
Disease severity
Dna sequence
Enzyme linked immunosorbent assay
Exon
Fat mass
Female
Gene
Gene deletion
Gene insertion
Hirsutism
Homozygosity
Human
Hypertriglyceridemia
Insulin resistance
Knee pain
Lep gene
Lepr gene
Leptin deficiency
Mc4r gene
Missense mutation
Morbid obesity
Nail hypoplasia
Next generation sequencing
Pcsk1 gene
Pedigree
Physical examination
Point mutation
Pomc gene
Pparg gene
Preschool child
Protein blood level
School child
Sleeve gastrectomy
Strabismus
Telangiectasia
Walking
Young adult
Colombian sisters
Congenital leptin deficiency
Consanguinity
Extreme obesity
Lep gene
Novel mutation
- Rights
- License
- Abierto (Texto Completo)
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dc.title.spa.fl_str_mv |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
title |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
spellingShingle |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity Estradiol Follitropin Gemfibrozil Genomic dna Glucose Hemoglobin a1c High density lipoprotein cholesterol Insulin Leptin Luteinizing hormone Metformin Prolactin Thyrotropin Triacylglycerol Acne Adolescent Adult Amenorrhea Article Body mass Body weight gain Case report Child Childhood obesity Clinical article Clinical feature Clinodactyly Colombian Consanguinity Dietary intake Disease severity Dna sequence Enzyme linked immunosorbent assay Exon Fat mass Female Gene Gene deletion Gene insertion Hirsutism Homozygosity Human Hypertriglyceridemia Insulin resistance Knee pain Lep gene Lepr gene Leptin deficiency Mc4r gene Missense mutation Morbid obesity Nail hypoplasia Next generation sequencing Pcsk1 gene Pedigree Physical examination Point mutation Pomc gene Pparg gene Preschool child Protein blood level School child Sleeve gastrectomy Strabismus Telangiectasia Walking Young adult Colombian sisters Congenital leptin deficiency Consanguinity Extreme obesity Lep gene Novel mutation |
title_short |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
title_full |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
title_fullStr |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
title_full_unstemmed |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
title_sort |
Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity |
dc.subject.keyword.spa.fl_str_mv |
Estradiol Follitropin Gemfibrozil Genomic dna Glucose Hemoglobin a1c High density lipoprotein cholesterol Insulin Leptin Luteinizing hormone Metformin Prolactin Thyrotropin Triacylglycerol Acne Adolescent Adult Amenorrhea Article Body mass Body weight gain Case report Child Childhood obesity Clinical article Clinical feature Clinodactyly Colombian Consanguinity Dietary intake Disease severity Dna sequence Enzyme linked immunosorbent assay Exon Fat mass Female Gene Gene deletion Gene insertion Hirsutism Homozygosity Human Hypertriglyceridemia Insulin resistance Knee pain Lep gene Lepr gene Leptin deficiency Mc4r gene Missense mutation Morbid obesity Nail hypoplasia Next generation sequencing Pcsk1 gene Pedigree Physical examination Point mutation Pomc gene Pparg gene Preschool child Protein blood level School child Sleeve gastrectomy Strabismus Telangiectasia Walking Young adult Colombian sisters Congenital leptin deficiency Consanguinity Extreme obesity Lep gene Novel mutation |
topic |
Estradiol Follitropin Gemfibrozil Genomic dna Glucose Hemoglobin a1c High density lipoprotein cholesterol Insulin Leptin Luteinizing hormone Metformin Prolactin Thyrotropin Triacylglycerol Acne Adolescent Adult Amenorrhea Article Body mass Body weight gain Case report Child Childhood obesity Clinical article Clinical feature Clinodactyly Colombian Consanguinity Dietary intake Disease severity Dna sequence Enzyme linked immunosorbent assay Exon Fat mass Female Gene Gene deletion Gene insertion Hirsutism Homozygosity Human Hypertriglyceridemia Insulin resistance Knee pain Lep gene Lepr gene Leptin deficiency Mc4r gene Missense mutation Morbid obesity Nail hypoplasia Next generation sequencing Pcsk1 gene Pedigree Physical examination Point mutation Pomc gene Pparg gene Preschool child Protein blood level School child Sleeve gastrectomy Strabismus Telangiectasia Walking Young adult Colombian sisters Congenital leptin deficiency Consanguinity Extreme obesity Lep gene Novel mutation |
description |
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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. |
publishDate |
2019 |
dc.date.created.spa.fl_str_mv |
2019 |
dc.date.accessioned.none.fl_str_mv |
2020-05-26T00:09:13Z |
dc.date.available.none.fl_str_mv |
2020-05-26T00:09:13Z |
dc.type.eng.fl_str_mv |
article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.spa.spa.fl_str_mv |
Artículo |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.3390/genes10050342 |
dc.identifier.issn.none.fl_str_mv |
20734425 |
dc.identifier.uri.none.fl_str_mv |
https://repository.urosario.edu.co/handle/10336/24144 |
url |
https://doi.org/10.3390/genes10050342 https://repository.urosario.edu.co/handle/10336/24144 |
identifier_str_mv |
20734425 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.citationIssue.none.fl_str_mv |
No. 5 |
dc.relation.citationTitle.none.fl_str_mv |
Genes |
dc.relation.citationVolume.none.fl_str_mv |
Vol. 10 |
dc.relation.ispartof.spa.fl_str_mv |
Genes, ISSN:20734425, Vol.10, No.5 (2019) |
dc.relation.uri.spa.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072815955&doi=10.3390%2fgenes10050342&partnerID=40&md5=e37232448f2c599cb2e98c40362556e2 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
MDPI AG |
institution |
Universidad del Rosario |
dc.source.instname.spa.fl_str_mv |
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dc.source.reponame.spa.fl_str_mv |
reponame:Repositorio Institucional EdocUR |
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f043ad33-4ce9-4eac-be5b-449a77d7114a922b22e4-b494-425e-a9c9-35d229bd9881be9f5a35-54f8-413b-8e1b-d4c5e166d66ddba02873-8aac-4ddd-9cf0-6d0c81550703c5e6e108-62b4-4f57-924c-9fd4941d99c12438e53e-50b6-4a56-b8d0-6f0de4d885c488c470e3-4b46-4ce5-909f-52af61327d07a12bad51-985e-45af-9add-28423794bdaa39992d7b-7229-435d-81cf-06ced78bcb0ebff3f370-68f0-4f53-bad1-dbca3ebb9dab19331819600eaf79476-2bb2-4ef4-a91d-ab03db8b46a4a54dba97-7ff4-4f17-af61-21f771a5af4310548610e9dc9220-df51-48ab-a493-8c5b1f4033966b6971fc-81f6-4268-8de0-9735051bc4404bef98e7-a0f6-4cf8-a619-f68a8010b0d6c1fae85e-b13f-413d-aa6f-f1c5714c732e2020-05-26T00:09:13Z2020-05-26T00:09:13Z2019Background: 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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.application/pdfhttps://doi.org/10.3390/genes1005034220734425https://repository.urosario.edu.co/handle/10336/24144engMDPI AGNo. 5GenesVol. 10Genes, ISSN:20734425, Vol.10, No.5 (2019)https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072815955&doi=10.3390%2fgenes10050342&partnerID=40&md5=e37232448f2c599cb2e98c40362556e2Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocUREstradiolFollitropinGemfibrozilGenomic dnaGlucoseHemoglobin a1cHigh density lipoprotein cholesterolInsulinLeptinLuteinizing hormoneMetforminProlactinThyrotropinTriacylglycerolAcneAdolescentAdultAmenorrheaArticleBody massBody weight gainCase reportChildChildhood obesityClinical articleClinical featureClinodactylyColombianConsanguinityDietary intakeDisease severityDna sequenceEnzyme linked immunosorbent assayExonFat massFemaleGeneGene deletionGene insertionHirsutismHomozygosityHumanHypertriglyceridemiaInsulin resistanceKnee painLep geneLepr geneLeptin deficiencyMc4r geneMissense mutationMorbid obesityNail hypoplasiaNext generation sequencingPcsk1 genePedigreePhysical examinationPoint mutationPomc genePparg genePreschool childProtein blood levelSchool childSleeve gastrectomyStrabismusTelangiectasiaWalkingYoung adultColombian sistersCongenital leptin deficiencyConsanguinityExtreme obesityLep geneNovel mutationCongenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesityarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Yupanqui-Lozno, HernanBastarrachea, Raul A.Yupanqui-Velazco, Maria E.Alvarez-Jaramillo, MonicaMedina-Méndez, EstebanGiraldo-Peña, Aida P.Arias-Serrano, AlexandraTorres-Forero, CarolinaGarcia-Ordoñez, Angelica M.Mastronardi, Claudio A.Restrepo Fernández, Carlos MartínRodriguez-Ayala, ErnestoNava-Gonzalez, Edna J.Arcos-Burgos, MauricioKent, Jack W.Cole, Shelley A.Licinio, JulioCelis-Regalado, Luis G.ORIGINALgenes-10-00342.pdfapplication/pdf1170961https://repository.urosario.edu.co/bitstreams/4f7f6c4e-32a4-4305-908a-8ad868e0dbd9/downloadedae61d4c7a808efe5b9d33ff62c2177MD51TEXTgenes-10-00342.pdf.txtgenes-10-00342.pdf.txtExtracted texttext/plain51258https://repository.urosario.edu.co/bitstreams/9c9801ac-e7c4-4c24-be8e-c81568389868/download1c798dd93f079f78c3e3b8c397104827MD52THUMBNAILgenes-10-00342.pdf.jpggenes-10-00342.pdf.jpgGenerated Thumbnailimage/jpeg4924https://repository.urosario.edu.co/bitstreams/5012e613-8c9d-46cc-bceb-db90f603e5d5/download1e1ca3803ffd194bc52cb9d131bedff9MD5310336/24144oai:repository.urosario.edu.co:10336/241442022-05-02 07:37:17.084355https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co |