A new mutation c.422C&gt;G (p.S141C) in homoand heterozygous forms of the human leptin gene

Chekhranova, M. K.; Karpova, S. K.; Yatsyshina, S. B.; Pankov, J. A.

doi:10.1134/s1068162008060198

Cited by 21 publications

(26 citation statements)

References 6 publications

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“…13374delGFrameshiftGly-ValPakistaniYes2Montague et al [16]g13289C>TMissenseArg-TrpTurkishYes3Strobel et al [15]g. 13398C>GMissenseSer-CysTurkmenianUnknownUnknownChekhranova et al [24]g. 13285C>AMissenseAsn-LysEgyptianYes2Mazen et al [23]g.…”

Section: Discussionmentioning

confidence: 99%

The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan

Shabana

Hasnain

2016

Biol Res

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BackgroundObesity is a complex disorder and has been increasing globally at alarming rates including Pakistan. However, there is scarce research on understanding obesity genetics in Pakistan. Leptin is a hormone secreted by adipocytes in response to satiety and correlates with body weight. Any mutations in the LEP gene have an adverse effect on energy regulation pathway and lead to severe, early onset obesity. To date, only eight mutations have been described in the LEP gene of which p. N103K is one.MethodsWe aimed to analyze the prevalence of this mutation in Pakistani subjects. A total of 475 subjects were genotyped by PCR–RFLP analysis and their serum profiling was done.ResultsResults showed that this mutation was present only in one male child with early onset obesity (10 year). He had very low serum leptin levels suggestive of functional impact of the mutation. The prevalence of such mutations is, however, low due to the drastic effects on the energy regulation.ConclusionIn conclusion, LEP gene mutations contribute significantly to the monogenic forms of obesity and are important due to the availability of treatment options. Such mutations may exert their effect by directly affecting energy regulation pathway and are more prominent in the early stages of life only.

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Section: Discussionmentioning

confidence: 99%

The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan

Shabana

Hasnain

2016

Biol Res

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“…Seven additional mutations have since been reported. [3][4][5][6][7][8] The type I cytokine leptin is mainly produced by adipocytes to signal the energy state of the body and exerts its function as a satiety signal in the hypothalamus. 9 Clinical hallmarks of congenital leptin deficiency include early-onset extreme obesity, marked hyperphagia, and hormonal as well as metabolic disturbances.…”

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confidence: 99%

Biologically Inactive Leptin and Early-Onset Extreme Obesity

et al. 2015

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Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss.

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“…The first frameshift homozygous LEP mutation resulting in truncated transcription of leptin was discovered in two severely obese cousins within a highly consanguineous Pakistani family (104). Eight other pathogenic mutations were subsequently reported in probands from consanguineous families in Pakistan (103,(105)(106)(107)(108)(109)(110), India (111), Turkey (112)(113)(114), Egypt (115), Turkmenistan (116) and from a non-consanguineous family in Austria (117) ( Table 1). These subjects presented with no detectable circulating leptin, due to truncated transcription of leptin.…”

Section: Non-syndromic Monogenic Obesitymentioning

confidence: 99%

Obesity genetics: insights from the Pakistani population

et al. 2017

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The Pakistani population is extensively diverse, indicating a genetic admixture of European and Central/West Asian migrants with indigenous South Asian gene pools. Pakistanis are organized in different ethnicities/castes based on cultural, linguistic and geographical origin. While Pakistan is facing a rapid nutritional transition, the rising prevalence of obesity is driving a growing burden of health complications and mortality. This represents a unique opportunity for the research community to study the interplay between obesogenic environmental changes and obesity predisposing genes in the time frame of one generation. This review recapitulates the ancestral origins of Pakistani population, the societal determinants of the rise in obesity and its governmental management. We describe the contribution of syndromic, monogenic non-syndromic and polygenic obesity genes identified in the Pakistani population. We then discuss the utility of gene identification approaches based on large consanguineous families and original gene × environment interaction study designs in discovering new obesity genes and causal pathways. Elucidation of the genetic basis of obesity in the Pakistani population may result in improved methods of obesity prevention and treatment globally.

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A new mutation c.422C>G (p.S141C) in homoand heterozygous forms of the human leptin gene

Cited by 21 publications

References 6 publications

The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan

The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan

Biologically Inactive Leptin and Early-Onset Extreme Obesity

Obesity genetics: insights from the Pakistani population

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