PMC6293235_01
PMC6293235_02
Simplified depiction of the LEPR gene and the extracellular domain of the mature LEPR protein and visualization of mutations in the human LEPR protein. Transmembrane and cytoplasmatic domains are not depicted, as no human mutations have been described in these domains. Every exon is numbered and assigned to the domain it encodes in the LEPR protein (the structure of the LEPR protein is based on the information of Peelman et al.). The functional relevance of LEPR domains is given. LEP interacting sites are marked by white or black lines in the protein sketch and are positioned in CRHI/immunoglobulin-like domain (p.L372, A409, Y411, H419, H420) and CRHII (p.L471, Y472, F500, IFLL503-506, F563). Positions of WSXWS motifs are depicted as green lines: 319 to 323 and 622 to 626. Colored dots indicate and type affected protein position of human LEPR mutations; mutations result in single amino acid changes (green dots), or a truncated protein (red dots). BS, binding site; IGD, immunoglobulin-like domain; p., amino acid position in the protein.
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F1
Structurally, all isoforms share the same extracellular domain with an 820-amino acid (aa) length (Fig. 1). The extracellular domain is divided into six subdomains (Fig. 1). LEPR immunoglobulin-like domain (Fig. 1). LEPR activation furthermore requires the two fibronectin type III (FNIII) domains in membrane proximity. Detailed information is given in Table 2 and Table 3 and Fig. 1.
Body fat percentages, BMI z scores, and serum LEP concentrations in patients with biallelic LEPR mutations. (A) Body fat percentage by sex (mean age females, 18.2 y; mean age males, 10.1 y; median females, 54.7%; median males 48.7%). (B) BMI z score by sex (mean age females, 15.8 y; mean age males, 7.8 y; median females, 4.95; median males, 4.5). (C) Serum LEP concentrations by sex (mean age females, 17.2 y; mean age males, 8.0 y; median females, 93.5 microg/L; median males, 58.4 microg/L). (D) Correlation of body fat percentage and serum LEP concentrations in females (mean age, 19.4 y; n = 9). (E) Correlation of body fat percentage and serum LEP concentrations in males (mean age, 10.1 y; n = 11).
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F2
However, this comparison is limited by the large age difference between the groups (Fig. 2D and 2E).
PMC6293235_03
Body fat percentages, BMI z scores, and serum LEP concentrations in patients with biallelic LEPR mutations. (A) Body fat percentage by sex (mean age females, 18.2 y; mean age males, 10.1 y; median females, 54.7%; median males 48.7%). (B) BMI z score by sex (mean age females, 15.8 y; mean age males, 7.8 y; median females, 4.95; median males, 4.5). (C) Serum LEP concentrations by sex (mean age females, 17.2 y; mean age males, 8.0 y; median females, 93.5 microg/L; median males, 58.4 microg/L). (D) Correlation of body fat percentage and serum LEP concentrations in females (mean age, 19.4 y; n = 9). (E) Correlation of body fat percentage and serum LEP concentrations in males (mean age, 10.1 y; n = 11).
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F2
However, this comparison is limited by the large age difference between the groups (Fig. 2D and 2E).