PDF(Pubmed)
Abstract：
Congenital hypogonadotropic hypogonadism (CHH) is a genetically and clinically diverse disorder encompassing Kallmann syndrome (KS) and normosmic CHH (nCHH). Although mutations in numerous genes account for nearly 50% of CHH cases, a significant portion remains genetically uncharacterized. While most mutations follow the traditional Mendelian inheritance patterns, evidence suggests oligogenic interactions between CHH genes, acting as modifier genes to explain variable expressivity and incomplete penetrance associated with certain mutations.In this study, the proband presented with nCHH, while his son exhibited KS. We employed whole-exome sequencing (WES) to investigate the genetic differences between the two, and Sanger sequencing was used to validate the results obtained from WES.Genetic analysis revealed that both the proband and his son harboured a mutation in FGFR1 gene. Notably, an additional rare mutation in PROKR2 gene was exclusively identified in the son, which suggests the cause of the phenotypic difference between KS and nCHH.
摘要：
先天性低促性腺激素性性腺功能减退症（CHH）是一种遗传和临床上多样化的疾病，包括卡尔曼综合征（KS）和正常CHH（nCHH）。尽管许多基因的突变占CHH病例的近50％，很大一部分仍然没有遗传特征。虽然大多数突变遵循传统的孟德尔遗传模式，证据表明CHH基因之间的寡基因相互作用，充当修饰基因来解释与某些突变相关的可变表达和不完全外显率。在这项研究中,带有nCHH的先证者，而他的儿子展示了KS。我们采用全外显子组测序（WES）来研究两者之间的遗传差异，和Sanger测序用于验证从WES获得的结果。遗传分析表明，先证者和他的儿子都具有FGFR1基因的突变。值得注意的是,PROKR2基因中的另一个罕见突变仅在儿子中发现，这表明KS和nCHH之间表型差异的原因。
