Hypogonadotropic hypogonadism in a trisomy X carrier: phenotype description and genotype correlation

Abstract

We report on a 31-year old female who presented at genetic counseling for a small uterus, secondary amenorrhea and sterility. Gonadotropic hormone levels were low, suggesting a Hypogonadotropic Hypogonadism (HH) condition. Cytogenetic analysis demonstrated the presence of Trisomy X associated to an interstitial deletion of chromosome 4q13.2, resulting in the complete loss of a copy of the GNRHR gene. As GNRHR is known to be responsible for an autosomal recessive form of HH, we checked the status of the undeleted allele and we found the Q106R substitution. In conclusion, the results of our cytogenetic and molecular analyses have allowed us to clarify the etiology of the patient's condition.

Chinese abstract

我们报道了一位31岁的女性，她因子宫小，继发性闭经和不孕进行遗传学咨询。低促性腺素水平表明了性腺机能减退的状况（HH）。细胞遗传学分析表明了X三体表型与染色体4q13.2的中间缺失有关，导致了促性腺激素释放激素受体（GNRHR）基因拷贝的全部缺失。既然GNRHR是HH常染色体隐性遗传的一种表现形式，我们检测了等位基因的修复情况，发现Q106R被替换。总之，我们的细胞遗传学和分子生物学分析使得我们可以明确患者病情的病因。

• 4q13.2
• deletion
• genetic counseling
• GNRHR
• Hypogonadotropic hypogonadism
• trisomy X

Acknowledgements

We gratefully acknowledge Prof Carlo Flamigni, Dr Andrea Zacutti and Dr Pierangela De Biasio for their excellent expertise, professional support and discussion. We thank Corrado Torello for technical assistance and Claudia Cocco for critical reading of the manuscript.

Declaration of interest

The authors report no declarations of interest.

We acknowledge co-funding from “Cinque per mille” and “Ricerca corrente” (Italian Ministry of Health).