摘要
目的报告1例家族性男性性早熟（familial male-limited precocious puberty，FMPP）患儿的临床特点，并对其黄体生成素受体基因（LHCGR）进行突变分析。方法收集1例3．1岁FMPP患儿的临床资料，包括性征检查、促性腺激素释放激素兴奋试验、血清睾酮检测及骨龄检查等。对患儿及其父母外周血白细胞LHCGR基因的11个外显子进行PCR扩增和DNA直接测序。结果患儿为男性，身高116．8cm（＋5．1s），外阴发育2期，双侧睾丸8mL，阴茎8．5cm×2．5cm，睾酮2310ng／L，骨龄9岁，垂体兴奋试验显示黄体生成素峰值2．66IU／L，卵泡刺激素峰值1．03IU／L，符合外周性性早熟的临床表现。PCR扩增片段直接测序显示患儿LHCGR基因第11外显子1703C〉T突变，导致568位氨基酸由丙氨酸替换为缬氨酸。用芳香化酶抑制剂半年后，患儿的骨龄得到控制。患儿父亲检测到相同的基因突变位点，但未出现青春发育异常。结论FMPP是外周性性早熟的罕见病因。本病例有典型的临床表现，检测发现其LHCGR基因杂合突变C．1703C〉T（Ala568Val），为国内首次发现。父子具有相同突变基因但表型不同，提示FMPP具有不一致的表现度。
Objective Familial male-limited precocious puberty （FMPP） is due to constitutive activation of a mutant luteinizing hormone/choriogonadotropin receptor （LH/CGR） leading to elevated testosterone synthesis in testicular Leydig cells. In the present study, we have analyzed the LHCGR gene for members of a Chinese FMPP family. Methods Physical examinations have included assessment of penile length, testicular volume and pubic hair. Bone age assessment, levels of testosterone and gonadotropin- releasing hormone （GnRH） stimulations tests were measured. DNA was extracted from blood samples of the proband and his parents using an QIAGEN Blood DNA Mini Kit. The 11 exons of LHCGR gene were amplified using an AmpliTaq PCR system, and the PCR products were sequenced using an ABI3130xl Genetic Analyzer. Results The affected boy was 3 year and 1 month old and showed typical clinical manifestation of peripheral precocious puberty. His height was 116.8cm （＋5. 1s） and Tanner stages were PH2. Testicular volume was 8 mL bilaterally, penile was 8.5cm× 2.5cm. Basal testosterone was 2310 ng/ L and bone age was 9 years. GnRH stimulation test revealed a prepubertal response to gonadotropin. The peak of LH was 2. 66 IU/L, and the peak of FSH was 1. 03 IU/L. Upon sequencing exon 11 of the LHCGR, a heterozygous point mutation of nucleotide 1703 from C to T was detected, which resulted in an amino acid transition from Ala （GCC） to Val （GTC） at position 568. Thus the mutation of LHCGR gene was confirmed to be constitutively active. After treating with aromatase inhibitors for half a year, the patient showed an increase in bone age and height by half a year and 4 cm, respectively. The same point mutation was detected in the patient＇s father, but did not have any influence on his puberty development. Conclusion A novel point mutation of the LHCGR gene has been identified in a family affected with FMPP. The c. 1703C〉T mutant LHCGR was confirmed to be constitutively active, which has led to maturation and proliferation of Leydig cells. The variable phenotype within the family suggested variable expressivity of the disease.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2012年第6期631-634,共4页
Chinese Journal of Medical Genetics
关键词
家族性男性性早熟
LHCGR基因
激活突变
序列分析
表现度
Familial male-limited precocious puberty
LHCGR gene
Activating mutation
Sequence analysis
Expressivity
