Ayşehan Akıncı1, Doğa Türkkahraman2, İbrahim Tekedereli3, Leyla Özer4, Bahri Evren5, İbrahim Şahin5, Tarkan Kalkan6, Yusuf Çürek2, Emine Çamtosun1, Esra Döğer7, Aysun Bideci7, Ayla Güven8, Erdal Eren9, Özlem Sangün10, Atilla Çayır11, Pelin Bilir12, Ayça Törel Ergür13, Oya Ercan14. 1. İnönü University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Malatya, Turkey 2. Antalya Training and Research Hospital, Clinic of Pediatric Endocrinology and Diabetes, Antalya, Turkey 3. İnönü University Faculty of Medicine, Department of Molecular Genetics, Malatya, Turkey 4. Yüksek İhtisas University Faculty of Medicine, Department of Molecular Genetics, Ankara, Turkey 5. İnönü University Faculty of Medicine, Department of Endocrinology and Diabetes, Malatya, Turkey 6. Antalya Training and Research Hospital, Clinic of Molecular Genetics, Antalya, Turkey 7. Gazi University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Ankara, Turkey 8. Göztepe Training and Research Hospital, Clinic of Pediatric Endocrinology and Diabetes, İstanbul, Turkey 9. Uludağ University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Bursa, Turkey 10. Başkent University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Adana, Turkey 11. Erzurum Training and Reseach Hospital, Clinic of Pediatric Endocrinology and Diabetes, Erzurum, Turkey 12. Ankara University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Ankara, Turkey 13. Ufuk University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Ankara, Turkey 14. İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Departments of Pediatric Endocrinology and Diabetes, and Adolescent, İstanbul, Turkey
Abstract
Objective: Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, particularly if patients do not exibit any physical abnormalities or developmental delay. The aim of this study was to screen 41 different obesity-related genes in children with non-syndromic early onset severe obesity. Methods: Children with severe (body mass index-standard deviation score >3) and early onset (<7 years) obesity were screened by next-generation sequencing based, targeted DNA custom panel for 41 known-obesity-related genes and the results were confirmed by Sanger technique. Results: Six novel variants were identified in five candidate genes in seven out of 105 children with severe obesity; two in SIM1 (p.W306C and p.Q36X), one in POMC (p.Y160H), one in PCSK1 (p.W130G fs Ter8), two in MC4R (p.D126E) and one in LEPR (p.Q4H). Additionally, two previously known variations in MC4R were identified in four patients (p.R165W in three, and p.V166I in one). Conclusion: We identified six novel and four previously described variants in six obesity-related genes in 11 out of 105 childrens with early onset severe obesity. The prevalence of monogenic obesity was 10.4% in our cohort.
Objective: Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, particularly if patients do not exibit any physical abnormalities or developmental delay. The aim of this study was to screen 41 different obesity-related genes in children with non-syndromic early onset severe obesity. Methods:Children with severe (body mass index-standard deviation score >3) and early onset (<7 years) obesity were screened by next-generation sequencing based, targeted DNA custom panel for 41 known-obesity-related genes and the results were confirmed by Sanger technique. Results: Six novel variants were identified in five candidate genes in seven out of 105 children with severe obesity; two in SIM1 (p.W306C and p.Q36X), one in POMC (p.Y160H), one in PCSK1 (p.W130G fs Ter8), two in MC4R (p.D126E) and one in LEPR (p.Q4H). Additionally, two previously known variations in MC4R were identified in four patients (p.R165W in three, and p.V166I in one). Conclusion: We identified six novel and four previously described variants in six obesity-related genes in 11 out of 105 childrens with early onset severe obesity. The prevalence of monogenic obesity was 10.4% in our cohort.
Entities:
Keywords:
novel mutations; Early; onset; severe obesity
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