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

Objective: 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.

Design: Clinical study.

Setting: University hospital.

Patient(s): A 16-year-old girl with primary amenorrhea and poor breast development due to isolated FSH deficiency.

Intervention(s): Blood drawing before and after GnRH stimulation and pelvic ultrasound examination.

Main Outcome Measure(s): Gonadotropin and E(2) measurements and sequencing of the FSH beta-subunit gene.

Result(s): 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 beta-subunit.

Conclusion(s): The Tyr76X mutation of the FSH beta-subunit was associated with a partial phenotype of FSH deficiency. To date, only four loss-of-function mutations of the FSH beta-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 beta-subunit in both sexes.