The first case of novel variants of the FSHR mutation causing primary amenorrhea in 2 siblings in Korea.

IF 2.8 Q3 ENDOCRINOLOGY & METABOLISM
Sukdong Yoo, Ju Young Yoon, Changwon Keum, Chong Kun Cheon
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引用次数: 0

Abstract

Follicle-stimulating hormone receptor (FSHR) mutation is a rare cause of amenorrhea. We report the first case of FSHR mutations in Korea. Two female siblings, aged 16 (patient 1) and 19 (patient 2) years, were referred to the pediatric endocrinology clinic because of primary amenorrhea despite normal breast budding. Gonadotropin-releasing hormone stimulation test showed markedly elevated luteinizing hormone and follicle-stimulating hormone with a relatively low level of estrogen, suggesting hypergonadotropic hypogonadism. Pelvic magnetic resonance imaging revealed a bicornuate uterus in patient 1 and uterine hypoplasia with thinning of the endometrium in patient 2. The progesterone challenge test revealed no withdrawal of bleeding. After two months of administration of combined oral contraceptives, menarche was initiated at regular intervals. To determine the genetic cause of amenorrhea in these patients, whole exome sequencing (WES) was performed, which revealed a compound heterozygous FSHR mutation, c.1364T>G (p.Val455Gly) on exon 10, and c.374T>G (p.Leu125Arg) on exon 4; both of which were novel mutations and were confirmed by Sanger sequencing. The patients maintained regular menstruation and improved bone mineral density while taking combined oral contraceptives, calcium, and vitamin D. Therefore, FSHR mutations can be the cause of amenorrhea in Koreans, and WES facilitates diagnosing the rare cause of amenorrhea.

Abstract Image

Abstract Image

在韩国的两个兄弟姐妹中,第一例新的FSHR突变变异导致原发性闭经。
促卵泡激素受体(FSHR)突变是一种罕见的闭经原因。我们报告了韩国第一例FSHR突变。两名年龄分别为16岁(患者1)和19岁(患者2)的女性兄弟姐妹,因乳房正常萌动而原发性闭经而被转介到儿科内分泌科诊所。促性腺激素释放激素刺激试验显示黄体生成素和促卵泡激素明显升高,雌激素水平相对较低,提示促性腺功能亢进症。盆腔磁共振成像显示患者1为双角状子宫,患者2为子宫发育不全伴子宫内膜变薄。孕酮激发试验未见出血停止。服用联合口服避孕药两个月后,定期开始月经初潮。为了确定这些患者闭经的遗传原因,我们进行了全外显子测序(WES),结果显示FSHR存在一个复合杂合突变,位于第10外显子的c.1364T>G (p.Val455Gly)和位于第4外显子的c.374T>G (p.Leu125Arg);这两个都是新的突变,并被桑格测序证实。患者在联合服用口服避孕药、钙和维生素d的同时,月经正常,骨密度提高。因此,FSHR突变可能是韩国人闭经的原因,而WES有助于诊断罕见的闭经原因。
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来源期刊
CiteScore
4.00
自引率
18.20%
发文量
59
审稿时长
24 weeks
期刊介绍: The Annals of Pediatric Endocrinology & Metabolism Journal is the official publication of the Korean Society of Pediatric Endocrinology. Its formal abbreviated title is “Ann Pediatr Endocrinol Metab”. It is a peer-reviewed open access journal of medicine published in English. The journal was launched in 1996 under the title of ‘Journal of Korean Society of Pediatric Endocrinology’ until 2011 (pISSN 1226-2242). Since 2012, the title is now changed to ‘Annals of Pediatric Endocrinology & Metabolism’. The Journal is published four times per year on the last day of March, June, September, and December. It is widely distributed for free to members of the Korean Society of Pediatric Endocrinology, medical schools, libraries, and academic institutions. The journal is indexed/tracked/covered by web sites of PubMed Central, PubMed, Emerging Sources Citation Index (ESCI), Scopus, EBSCO, EMBASE, KoreaMed, KoMCI, KCI, Science Central, DOI/CrossRef, Directory of Open Access Journals(DOAJ), and Google Scholar. The aims of Annals of Pediatric Endocrinology & Metabolism are to contribute to the advancements in the fields of pediatric endocrinology & metabolism through the scientific reviews and interchange of all of pediatric endocrinology and metabolism. It aims to reflect the latest clinical, translational, and basic research trends from worldwide valuable achievements. In addition, genome research, epidemiology, public education and clinical practice guidelines in each country are welcomed for publication. The Journal particularly focuses on research conducted with Asian-Pacific children whose genetic and environmental backgrounds are different from those of the Western. Area of specific interest include the following : Growth, puberty, glucose metabolism including diabetes mellitus, obesity, nutrition, disorders of sexual development, pituitary, thyroid, parathyroid, adrenal cortex, bone or other endocrine and metabolic disorders from infancy through adolescence.
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