Congenital leptin and leptin receptor deficiencies in nine new families: identification of six novel variants and review of literature.

Autor: Mazen IH; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., El-Gammal MA; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Elaidy AA; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Anwar GM; Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt., Ashaat EA; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Abdel-Ghafar SF; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Eltahrir Street, Dokki, Cairo, 12311, Egypt., Abdel-Hamid MS; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Eltahrir Street, Dokki, Cairo, 12311, Egypt. mohamadnrc@hotmail.com.
Jazyk: angličtina
Zdroj: Molecular genetics and genomics : MGG [Mol Genet Genomics] 2023 Jul; Vol. 298 (4), pp. 919-929. Date of Electronic Publication: 2023 May 04.
DOI: 10.1007/s00438-023-02025-1
Abstrakt: Early childhood obesity is a real public health problem worldwide. Identifying the etiologies, especially treatable and preventable causes, can direct health professionals toward proper management. Measurement of serum leptin levels is helpful in the diagnosis of congenital leptin and leptin receptor deficiencies which are considered important rare causes of early childhood obesity. The main aim of this study was to investigate the frequency of LEP, LEPR, and MC4R gene variants among a cohort of Egyptian patients with severe early onset obesity. The current cross-sectional study included 30 children who developed obesity during the first year of life with BMI > 2SD (for age and sex). The studied patients were subjected to full medical history taking, anthropometric measurements, serum leptin and insulin assays, and genetic testing of LEP, LEPR and MC4R. Disease causing variants in LEP and LEPR were identified in 10/30 patients with a detection rate of 30%. Eight different homozygous variants (two pathogenic, three likely pathogenic, and three variants of uncertain significant) were identified in the two genes, including six previously unreported LEPR variants. Of them, a new frameshift variant in LEPR gene (c.1045delT, p.S349Lfs*22) was recurrent in two unrelated families and seems to have a founder effect in our population. In conclusion, we reported ten new patients with leptin and leptin receptor deficiencies and identified six novel LEPR variants expanding the mutational spectrum of this rare disorder. Furthermore, the diagnosis of these patients helped us in genetic counseling and patients' managements specially with the availability of drugs for LEP and LEPR deficiencies.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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