两例瘦素受体突变型极端肥胖家系研究

摘要

本研究针对2例极端肥胖的经过代谢手术治疗减重效果不佳的瘦素受体(LEPR)突变女性患者进行报道.提取患者及父母的外周血基因组DNA,对患者及其家系进行分子遗传学分析,发现了LEPR基因的3个致病突变,这3个突变位点均未被报道.2例患者均因“自幼多食、体重增长过快”就诊.患者1,女性,39岁,身高150 cm,体重130 kg,体重指数(BMI) 57.8 kg/m2.血瘦素156.4 μg/L,基因检测发现患者1的LEPR基因15号外显子存在c.2317G＞T纯合突变,患者父亲和母亲均携带c.2317G＞T杂合突变.患者2,女性,37岁,身高158 cm,体重167 kg,BMI67.0 kg/m2.血瘦素193.4μg/L,基因检测结果显示患者2的LEPR基因10号外显子存在c.1482delT杂合突变,同时其12号外显子存在c.1892C＞A杂合突变,该突变位点与关键酶的活性位点相关.父亲携带c.1482delT杂合突变,母亲携带c.1892C＞A杂合突变.2例患者均行外科减重治疗,在手术后的半年体重分别下降约22 kg和40 kg,但后续随访显示患者1体重在术后2年反弹至原体重,而患者2体重在后续半年也不再进一步下降.%This study reported two women with extreme obesity who underwent metabolic surgery due to their mutations in leptin receptor (LEPR).Genomic DNA was extracted from the anticoagulant blood samples of the two patients and their parents.A panel of genes related to metabolic diseases or whole exon sequencing was screened and the results were confirmed by Sanger sequencing.This is the first time that these three mutations in LEPR were reported.Two patients complained insatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with height 150 cm,weight 130 kg,and BMI 57.8 kg/m2.Serum leptin level was 156.4 μg/L.A homozygous mutation of c.2317G＞T was found in exon 15 of LEPR gene in patient 1,which was descended from her father and mother respectively.Patient 2 was a 37-year-old woman with height 158 cm,weight 167 kg,and BMI 67 kg/m2.Serum leptin level was 193.4 μg/L.Genetic analysis showed compound heterozygous mutations of c.1482delT and c.1892C ＞ A.Her father showed heterozygous c.1482delT mutation,and her mother carried heterozygous c.1892C ＞ A mutation.Two patients all underwent metabolic surgery with body weight reduction of about 22 kg and 40 kg respectively after first six months.However,the follow-up studies showed that the body weight of patient 1 rebounded to pre-surgery level in two years and patient 2 did not further lose weight in the following six months.