CAJ | 학술논문

目的阐明1个家族性男性性早熟(familial male-limited precocious puberty)家系的黄体生成素(luteinizing hormone,LH)受体基因的突变状态,增加对LH受体激活突变导致男性性早熟发病机制的认识.方法 (1)描述1例5岁男孩假性性早熟患者临床表现、辅助检查特点和治疗过程;(2)对患者及其父母外周血白细胞LH受体基因的11个外显子进行 PCR扩增和DNA自接测序,同时对20例正常男性LH受体基因的外显子进行测定.结果 (1)患者临床确诊为男性假性性早熟,应用芳香化酶抑制剂后,身高增长速度减缓;(2)患者及其母亲LH受体基因存在杂合突变,c1193 T→C,导致398位的甲硫氨酸变为苏氨酸(M398T),持续性激活LH受体;(3)患者及其父母和20例正常男性均存在c935 A→G和c1065 T→C碱基改变.结论 (1)生殖细胞系LH受体基因杂合突变(c1193 T→C,M398T)导致LH受体功能持续激活,不断刺激睾丸Leydig细胞分泌雄激素,引起非LH依赖性男性性早熟的临床表现;(2)患者母亲存在相同杂合突变,但无异常临床表现,表明女性可为本病携带者,能将突变基因传给子代,但仅限男性患病;(3)汉族人群LH受体基因可能存在多态性.
목적 천명1개가족성남성성조숙(familial male-limited precocious puberty)가계적황체생성소(luteinizing hormone,LH)수체기인적돌변상태,증가대LH수체격활돌변도치남성성조숙발병궤제적인식.방법 (1)묘술1례5세남해가성성조숙환자림상표현、보조검사특점화치료과정;(2)대환자급기부모외주혈백세포LH수체기인적11개외현자진행 PCR확증화DNA자접측서,동시대20례정상남성LH수체기인적외현자진행측정.결과 (1)환자림상학진위남성가성성조숙,응용방향화매억제제후,신고증장속도감완;(2)환자급기모친LH수체기인존재잡합돌변,c1193 T→C,도치398위적갑류안산변위소안산(M398T),지속성격활LH수체;(3)환자급기부모화20례정상남성균존재c935 A→G화c1065 T→C감기개변.결론 (1)생식세포계LH수체기인잡합돌변(c1193 T→C,M398T)도치LH수체공능지속격활,불단자격고환Leydig세포분비웅격소,인기비LH의뢰성남성성조숙적림상표현;(2)환자모친존재상동잡합돌변,단무이상림상표현,표명녀성가위본병휴대자,능장돌변기인전급자대,단부한남성환병;(3)한족인군LH수체기인가능존재다태성.
Objective To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. Methods ( 1 ) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. Results (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother:c1193 T→C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A→ G (N312S) and c1065 T→C(same sense mutation). Conclusions (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.