Clinical and hormonal features of selective follicle-stimulating hormone (FSH) deficiency due to FSH beta-subunit gene mutations in both sexes

• Published in: Fertility and sterility Vol. 83; no. 2; pp. 466 - 470
• Main Authors: Berger, Karina, Souza, Haroldo, Brito, Vinicius Nahime, d'Alva, Catarina Brasil, Mendonca, Berenice Bilharinho, Latronico, Ana Claudia
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2005; Elsevier Science
• Subjects: Adolescent; Adult; Amenorrhea - blood; Amenorrhea - genetics; Amino Acid Substitution; Biological and medical sciences; Female; Follicle Stimulating Hormone, beta Subunit - blood; Follicle Stimulating Hormone, beta Subunit - deficiency; Follicle Stimulating Hormone, beta Subunit - genetics; FSH deficiency; FSH β-subunit gene; gonadotropins; Gynecology. Andrology. Obstetrics; Humans; Infertility, Female - blood; Infertility, Female - genetics; Infertility, Male - blood; Infertility, Male - genetics; Male; Medical sciences; Phenotype; Primary amenorrhea infertility; FSH β-subunit gene; gonadotropins; FSH deficiency; Primary amenorrhea infertility; Adenohypophyseal hormone; Gene; Fertility; Deficiency; Clinical form; Genetics; Gonadotropin; Mutation; Subunit; Follicle stimulating hormone
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2004.06.069

To report the clinical, hormonal, and molecular features of a female adolescent with selective FSH deficiency. In addition, a complete review of previous cases is provided, focusing on hormonal aspects. Clinical study. University hospital. A 16-year-old girl with primary amenorrhea and poor breast development due to isolated FSH deficiency. Blood drawing before and after GnRH stimulation and pelvic ultrasound examination. Gonadotropin and E 2 measurements and sequencing of the FSH β-subunit gene. The patient was referred for primary amenorrhea and partial breast development (Tanner III). Her basal and GnRH-stimulated LH levels were elevated (31 IU/L and 98 IU/L, respectively), whereas her FSH levels were undetectable (<1 IU/L) in both conditions. Estradiol levels were low (<13 pg/mL). Automatic sequencing showed a nucleotide substitution of C for A in exon 3, resulting in a homozygous nonsense mutation in amino acid position 76 (Tyr76X) of the FSH β-subunit. The Tyr76X mutation of the FSH β-subunit was associated with a partial phenotype of FSH deficiency. To date, only four loss-of-function mutations of the FSH β-subunit have been described in eight patients with undetectable serum FSH and high serum LH levels. Therefore, this unusual hormonal profile strongly suggests a defect in the FSH β-subunit in both sexes.