Startseite Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing
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Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing

  • Özlem Nalbantoğlu EMAIL logo , Filiz Hazan , Sezer Acar , Semra Gürsoy und Behzat Özkan
Veröffentlicht/Copyright: 8. Juli 2022
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 35 Heft 8

Abstract

Objectives

Non-syndromic monogenic obesity is a rare cause of early-onset severe obesity in the childhood period. The aim of this study was to screen four obesity related genes (LEP, LEPR, MC4R and POMC) in children and adolescents who had severe, non-syndromic early onset obesity.

Methods

Next-generation sequencing of all exons in LEP, LEPR, MC4R and POMC was performed in 154 children and adolescents with early onset severe obesity obesity.

Results

Fifteen different variants in nineteen patients were identified with a variant detection rate of 12.3%. While six different heterozygous variants were observed in MC4R gene (10/154 patients; 6.5%), five different variants in POMC gene (four of them were heterozygous and one of them was homozygous) (6/154 patients; 3.9%) and four different homozygous variants in LEPR gene (3/154 patients; 1.9%) were described. However, no variants were detected in the LEP gene. The most common pathogenic variant was c.496G>A in MC4R gene, which was detected in four unrelated patients. Six novel variants (6/15 variants; 40%) were described in seven patients. Four of them including c.233C>A and c.752T>C in MC4R gene and c.761dup and c.1221dup in LEPR gene were evaluated as pathogenic or likely pathogenic.

Conclusions

In conclusion, MC4R variants are the most common genetic cause of monogenic early-onset obesity, consistent with the literature. The c.496G>A variant in MC4R gene is highly prevalent in early-onset obese patients.

Keywords: childhood obesity; LEPR ; MC4R ; non-syndromic; POMC
Corresponding author: Özlem Nalbantoğlu, MD, Clinic of Pediatric Endocrinology, University of Health Sciences Turkey, Dr. BehçetUz Child Disease and Pediatric Surgery Training and Research Hospital, İsmet Kaptan Mh, Sezer Doğan Sokağı No:11 35210, İzmir, Turkey, Phone: +90 0232 411 60 00 (extension number: 6318), Fax: +90 0232 489 23 15, E-mail: .

Acknowledgments

We would like to thank the children and their parents who participated in this study.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2022-01-15
Accepted: 2022-06-16
Published Online: 2022-07-08
Published in Print: 2022-08-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Review Article
  3. Effects of vitamin D supplementation on glycemic control of children and adolescents with type 1 diabetes mellitus: a systematic review
  4. Original Articles
  5. A preliminary study on the relationship between environmental endocrine disruptors and precocious puberty in girls
  6. Tissue concentration of aldosterone in fetal adrenals of intrauterine death cases
  7. Complications of orthopedic treatment in patients diagnosed with X-linked hypophosphatemic rickets
  8. Comparison of insulin sensitivity indices for detection of double diabetes in Indian adolescents with type 1 diabetes
  9. Evaluation of the growth and nutritional status of preschool children: a pilot study in the cold area of China
  10. Arterial hypertension is associated with an increased risk of metabolic complications in pediatric patient with obesity
  11. From pregnancy to breastfeeding: adequate maternal body mass index is essential to prevent a high body mass index in your children
  12. Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing
  13. The association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness in children with obesity: a cross-sectional study
  14. Comprehensive assessment of cardiovascular disease risk in children with short stature due to isolated growth hormone deficiency: a case-control study
  15. Visceral adiposity is related to insulin sensitivity and inflammation in adolescents with obesity and mild sleep disordered breathing
  16. Recurrent hypoglycemic seizure as a presenting symptom of post-TBI hypopituitarism in children: a case report, review and proposed protocol
  17. Evaluation of the etiological and clinical characteristics of pediatric central diabetes insipidus
  18. Case Reports
  19. Clinical and radiologic evaluation of a Turkish family with hypochondroplasia and a rare FGFR3 variant
  20. Rituximab therapy in ROHHAD(NET) syndrome
  21. Ectopic parathyroid hormone as a rare aetiology of hypercalcemia with rhabdomyosarcoma: a new treatment strategy with zoledronic acid and Denosumab
  22. A 2-bp deletion mutation in SMPD1 gene leading to lysosomal acid sphingomyelinase deficiency in a Chinese consanguineous pedigree
https://doi.org/10.1515/jpem-2022-0027
Schlagwörter für diesen Artikel
childhood obesity; LEPR; MC4R; non-syndromic; POMC

Artikel in diesem Heft

  1. Frontmatter
  2. Review Article
  3. Effects of vitamin D supplementation on glycemic control of children and adolescents with type 1 diabetes mellitus: a systematic review
  4. Original Articles
  5. A preliminary study on the relationship between environmental endocrine disruptors and precocious puberty in girls
  6. Tissue concentration of aldosterone in fetal adrenals of intrauterine death cases
  7. Complications of orthopedic treatment in patients diagnosed with X-linked hypophosphatemic rickets
  8. Comparison of insulin sensitivity indices for detection of double diabetes in Indian adolescents with type 1 diabetes
  9. Evaluation of the growth and nutritional status of preschool children: a pilot study in the cold area of China
  10. Arterial hypertension is associated with an increased risk of metabolic complications in pediatric patient with obesity
  11. From pregnancy to breastfeeding: adequate maternal body mass index is essential to prevent a high body mass index in your children
  12. Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing
  13. The association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness in children with obesity: a cross-sectional study
  14. Comprehensive assessment of cardiovascular disease risk in children with short stature due to isolated growth hormone deficiency: a case-control study
  15. Visceral adiposity is related to insulin sensitivity and inflammation in adolescents with obesity and mild sleep disordered breathing
  16. Recurrent hypoglycemic seizure as a presenting symptom of post-TBI hypopituitarism in children: a case report, review and proposed protocol
  17. Evaluation of the etiological and clinical characteristics of pediatric central diabetes insipidus
  18. Case Reports
  19. Clinical and radiologic evaluation of a Turkish family with hypochondroplasia and a rare FGFR3 variant
  20. Rituximab therapy in ROHHAD(NET) syndrome
  21. Ectopic parathyroid hormone as a rare aetiology of hypercalcemia with rhabdomyosarcoma: a new treatment strategy with zoledronic acid and Denosumab
  22. A 2-bp deletion mutation in SMPD1 gene leading to lysosomal acid sphingomyelinase deficiency in a Chinese consanguineous pedigree
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