Testicular Failure and Male Infertility in the Monogenic Mulibrey Nanism Disorder

Context: Few monogenic mutations causing human male infertility have been identified to date. Objective: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. Design, Setting, and Patients: Twenty-eight male MUL patients of the Finnish national cohort aged 8.7 to 50.0 yr (median age, 28.8) at the end of observation were followed for 10 yr beginning from 2000–2001. Main Outcome Measures: Clinical characteristics, reproductive hormone levels, semen quality, and testicular histology were assessed. Results: The external genital phenotype was normal. In childhood and prepuberty, serum levels of FSH, LH, testosterone (T), and inhibin B were normal. Puberty started spontaneously at a median age of 12.6 yr (range, 11.1–15.0), and FSH, LH, T, and inhibin B levels increased adequately until midpuberty. Thereafter, testicular growth and virilization proceeded slowly. Concomitantly, FSH, and to a lesser extent LH, showed a progressive increase to hyp...