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Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database
Homozygosity for pathogenic variants in the leptin gene leads to congenital leptin deficiency causing severe early-onset obesity. This monogenic form of obesity has mainly been detected in patients from consanguineous families. Prevalence estimates for the general population using the Exome Aggregat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484668/ https://www.ncbi.nlm.nih.gov/pubmed/36121795 http://dx.doi.org/10.1371/journal.pone.0266642 |
Sumario: | Homozygosity for pathogenic variants in the leptin gene leads to congenital leptin deficiency causing severe early-onset obesity. This monogenic form of obesity has mainly been detected in patients from consanguineous families. Prevalence estimates for the general population using the Exome Aggregation Consortium (ExAC) database reported a low frequency of leptin mutations. One in approximately 15 million individuals will be homozygous for a deleterious leptin variant. With the present study, we aimed to extend these findings utilizing the augmented Genome Aggregation Database (gnomAD) v2.1.1 including more than 140,000 samples. In total, 68 non-synonymous and 7 loss-of-function leptin variants were deposited in gnomAD. By predicting functional implications with the help of in silico tools, like SIFT, PolyPhen2 and MutationTaster2021, the prevalence of hetero- and homozygosity for putatively pathogenic variants (n = 32; pathogenic prediction by at least two tools) in the leptin gene were calculated. Across all populations, the estimated prevalence for heterozygosity for functionally relevant variants was approximately 1:2,100 and 1:17,830,000 for homozygosity. This prevalence deviated between the individual populations. Accordingly, people from East Asia and individuals of mixed ethnicities (‘Others’) were at greater risk to carry a possibly damaging leptin variant. Generally, this study emphasises the scarcity of pathogenic leptin variants in the general population with varying prevalence for distinct study groups. |
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