Analysis of extreme obesity in two pedigrees due to leptin receptor mutation

Objective This study reported two extremly obesewomen who underwent metabolic surgery due to their mutationsin leptin receptor ( LEPR). Genomic DNA wasextracted from the anticoagulant blood samples of the twopatients and their parents. A panel of genes related tometabolic diseases or whole exon sequencing wasscreened and the results were confirmed by Sanger sequencing.This was the first time that these three mutationsin LEPR were reported. Two patients complainedinsatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with a height150 cm,a weight 130 kg,and a BMI 57. 8 kg /m2 . Serumleptin level was 156. 4 μg /L. A homozygous mutationof c. 2317G > T was found in exon 15 of LEPR genein patient 1,which was descended from her father andmother respectively. Patient 2 was a 37-year-old womanwith a height 158 cm,a weight 167 kg,and a BMI67 kg /m2 . Serum leptin level was 193. 4 μg /L. Geneticanalysis showed compound heterozygous mutations of c.1482delT and c. 1892C > A. Her father showed heterozygousc. 1482delT mutation,and her mother carriedheterozygous c. 1892C > A mutation. Two patients all underwentmetabolic surgery with body weight a reductionof about 22 kg and 40 kg respectively after the first sixmonths. However,the follow-up studies showed that thebody weight of patient 1 rebounded to pre-surgery level intwo years and patient 2 did not further lose weight in thefollowing six months.