Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity

Molecular Genetics and Metabolism

Volumn 102, Issue 4, 2011, Pages 461-464

  Mazen, I ^a   El Gammal, M ^a   Abdel Hamid, M ^a   Farooqi, I S ^b   Amr, K ^a  

^a NATIONAL RESEARCH CENTRE   (Egypt)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Leptin receptor gene; Novel mutation; Obesity

Indexed keywords

LEPTIN; LEPTIN RECEPTOR;

AMINO ACID SUBSTITUTION; ARTICLE; CASE REPORT; CHILD; CHROMOSOME; CLINICAL EXAMINATION; CONTROLLED STUDY; DISEASE SEVERITY; EGYPT; FEMALE; HETEROZYGOTE; HOMOZYGOTE; HORMONE BLOOD LEVEL; HUMAN; MALE; MISSENSE MUTATION; MUTATIONAL ANALYSIS; OBESITY; ONSET AGE; POLYMERASE CHAIN REACTION; PRESCHOOL CHILD; PRIORITY JOURNAL; RECEPTOR GENE; RECURRENT INFECTION; RELATIVE; RESPIRATORY TRACT INFECTION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM;

BASE SEQUENCE; CASE-CONTROL STUDIES; CHILD, PRESCHOOL; CONSANGUINITY; EGYPT; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HOMOZYGOTE; HUMANS; HYPERPHAGIA; INSULIN; LEPTIN; MALE; MUTATION, MISSENSE; OBESITY; RECEPTORS, LEPTIN; SEQUENCE ANALYSIS, DNA;

EID: 79952631516     PISSN: 10967192     EISSN: 10967206     Source Type: Journal    
DOI: 10.1016/j.ymgme.2010.12.013     Document Type: Article

References (11)

1. Schwartz M.W., Woods S.C., Porte D., Seeley R.J., Baskin D.G. Central nervous system control of food intake. Nature 2000, 404:661-671.
2. Montague C.T., Farooqi I.S., Whitehead J.P., Soos M.A., Rau H., Wareham N.J., Sewter C.O., Digby J.E., Mohammed S.N., Hurst J.A., Cheetham C.H., Earley A.R., Barnett A.H., Prins J.B., O'Rahilly S. Congenital leptin deficiency is associated with severe early onset obesity in humans. Nature 1997, 387:903-907.
3. Clément K., Vaisse C., Lahlou N., Cabrol S., Pelloux V., Cassuto D., Gourmelen M., Dina C., Cambaz J., Lacorte J.M., Basdevant A., Bougnéres P., Lebouc Y., Froguel P., Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998, 392:398-401.
4. Ozata M., Ozdemir I.C., Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. Clin. Endocrinol. Metab. 1999, 84:3686-3695.
5. Farooqi I.S., Matarese G., Lord G.M., Keogh J.M., Lawrence E., Agwu C., Sanna V., Jebb S.A., Perna F., Fontana S., Lechler R.I., DePaoli A.M., O'Rahilly S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 2002, 110:1093-1103.
6. Mazen I., El-Gammal M., Abdel-Hamid M., Amr K. A novel homozygous missense mutation of the leptin gene (N103K) 3 in an obese Egyptian patient. Mol. Genet. Metab. 2009, 97:305-308.
7. Strobel A., Issad T., Camoin L., Ozata M., Strosberg A.D. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat. Genet. 1998, 18:213-215.
8. Farooqi I.S., Wangensteen T., Collins S., Kimber W., Matarese G., Keogh J.M., Lank E., Bottomley B., Lopez-Fernandez J., Ferraz-Amaro I., Dattani M.T., Ercan O., Myhre A.G., Retterstol L., Stanhope R., Edge J.A., McKenzie S., Lessan N., Ghodsi M., De Rosa V., Perna F., Fontana S., Barroso I., Undlien D.E., O'Rahilly S. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N. Engl. J. Med. 2007, 356:237-247.
9. Fong T.M., Huang R.R., Tota M.R., Mao C., Smith T., Varnerin J., Karpitskiy V.V., Krause J.E., Van der Ploeg L.H. Localization of leptin binding domain in the leptin receptor. Mol. Pharmacol. 1998, 53:234-240.
10. Zabeau L., Defeau D., Van der Heyden J., Iserentant H., Vandekerckhove J., Tavernier J. Functional analysis of leptin receptor activation using a Janus kinase/signal transducer and activator of transcription complementation assay. Mol. Endocrinol. 2004, 18:150-161.
11. Fischer-Posovszky P., von Schnurbein J., Moepps B., Lahr G., Strauss G., Barth T.F., Kassubek J., Mühleder H., Möller P., Debatin K.M., Gierschik P., Wabitsch M. A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness. Clin. Endocrinol. Metab. 2010, 95:2836-2840.