Early onset obesity due to a mutation in the human leptin receptor gene
Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2022-08-01
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| Series: | Endocrine Connections |
| Online Access: | https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM21-0124.xml |
| _version_ | 1818515440204251136 |
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| author | Carolina Chaves Teresa Kay João Anselmo |
| author_facet | Carolina Chaves Teresa Kay João Anselmo |
| author_sort | Carolina Chaves |
| collection | DOAJ |
| description | Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/ mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss. |
| first_indexed | 2024-12-11T00:28:54Z |
| format | Article |
| id | doaj.art-9211c721cec6498abdd294d8b707ec59 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-12-11T00:28:54Z |
| publishDate | 2022-08-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-9211c721cec6498abdd294d8b707ec592022-12-22T01:27:27ZengBioscientificaEndocrine Connections2049-36142022-08-01111510.1530/EDM-21-0124Early onset obesity due to a mutation in the human leptin receptor geneCarolina Chaves0Teresa Kay1João Anselmo2Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, PortugalDepartment of Medical Genetics, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, PortugalDepartment of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, PortugalLeptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/ mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM21-0124.xml |
| spellingShingle | Carolina Chaves Teresa Kay João Anselmo Early onset obesity due to a mutation in the human leptin receptor gene Endocrine Connections |
| title | Early onset obesity due to a mutation in the human leptin receptor gene |
| title_full | Early onset obesity due to a mutation in the human leptin receptor gene |
| title_fullStr | Early onset obesity due to a mutation in the human leptin receptor gene |
| title_full_unstemmed | Early onset obesity due to a mutation in the human leptin receptor gene |
| title_short | Early onset obesity due to a mutation in the human leptin receptor gene |
| title_sort | early onset obesity due to a mutation in the human leptin receptor gene |
| url | https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM21-0124.xml |
| work_keys_str_mv | AT carolinachaves earlyonsetobesityduetoamutationinthehumanleptinreceptorgene AT teresakay earlyonsetobesityduetoamutationinthehumanleptinreceptorgene AT joaoanselmo earlyonsetobesityduetoamutationinthehumanleptinreceptorgene |