A novel heterozygous intron mutation in SEMA7A causing kallmann syndrome in a female

Abstract

Kallmann syndrome (KS) is a rare inherited disorder, which has significantly genotypic and phenotypic heterogeneity. KS is clinically characterized by the combination of hypogonadotropic hypogonadism and hypo/anosmia. At present, there is no relevant report that intron mutation in SEMA7A gene helps induce KS. A 17-year-old Chinese female (46, XX) came to our department due to primary amenorrhea, who actually had hyposmia since her childhood. Hypogonadotropic hypogonadism was then detected. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were remarkably low. And estradiol level was extremely low. The laboratory test results were consistent with KS. A heterozygous point mutation of intron 13 in SEMA7A (NM_003612.3:c.1640-3C > A) was identified. The patient received the treatment of pulsatile gonadotropin-releasing hormone (GnRH) pump, which could imitate physiological ovarian stimulation, thus resulting in mature follicle and a peak of LH. The patient was injected subcutaneously every 90 min with a dose of 10 µg per pulse, which had bona efficacy. She acquired menarche at about 43 days after the treatment. We firstly report a case of KS caused by a novel mutation site in the intron of SEMA7A gene. We mainly provide insight into the clinical manifestations, genetic diagnosis and treatment of KS.

摘要

卡尔曼综合征（KS）是一种罕见的遗传性疾病, 具有明显的基因型异质性和表型异质性。KS的临床特征是低促性腺激素性腺功能减退伴有嗅觉缺失或减退。目前尚无有关SEMA7A基因内含子突变诱导KS的报道。一名17岁的中国女性（46, XX）由于原发性闭经于我科就诊, 她从小开始出现嗅觉减退。随后检测出低促性腺激素性腺功能减退, 患者促黄体生成素（LH）和卵泡刺激素（FSH）的水平非常低, 雌二醇水平极低。实验室检验结果与KS一致。患者SEMA7A内含子13的杂合点突变（NM_003612.3：c.1640-3C> A）。该患者接受了脉冲性促性腺激素释放激素（GnRH）泵的治疗, 该泵可以模仿卵巢的生理刺激, 从而诱导卵泡成熟和LH峰值。每90分钟皮下注射一次, 每次脉冲10 mg, 具有良好的疗效。治疗后约43天, 她出现了月经初潮。我们首先报道了由SEMA7A基因内含子中一个新的突变位点引起的KS病例。我们主要对KS的临床表现,遗传诊断和治疗的提出一些见解。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Kallmann syndrome
• SEMA7A
• intron mutation
• hyposmia
• hypogonadotropic hypogonadism

Acknowledgements

We deeply thank the professors of Department of MRI room, the Second Affiliated Hospital of Harbin Medical University, Harbin, China) for their help and support with the imaging diagnosis.

Disclosure statement

The authors declare that they have no conflicts of interest concerning this work.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [81770809].