Figure 1.

(a) Diagram of the C-terminus of MC4R (yellow) with the putative 8th helical region shown in orange. Early termination variants at Q307 and L328 (red) were found in our population. The ³¹⁵EIICC³¹⁹ region (bold) is part of the 8th helix on MC4R and may play a critical regulatory role in MC4R. (b) Median lifetime BMIs of non-carriers and individual patients with truncations at Q307 and L328 obtained from electronic health records and ages of the patients when the BMIs were recorded are reported. The follow-up for these patients was from 2–16 years. The box represents 25% and 75% quartiles and error bars are min and max for each patient. The dashed line is the median BMI for the cohort. The sex of each patient is denoted F for female or M for male. (c) Using available genetic data, we built limited pedigrees for two female (circle) carriers of Q307Ter. In both cases the Q307Ter variant co-segregates with higher BMI. Critically, the 59-year-old carrier, while not obese, had a BMI that was higher than her non-carrier daughter (28.1 vs 22.7 respectively).