Spermatogenic Failure, X-Linked, 2

A number sign (#) is used with this entry because of evidence that X-linked spermatogenic failure-2 (SPGFX2) is caused by hemizygous mutation in the TEX11 gene (300311) on chromosome Xq13.

For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).

Clinical Features

In 3 males in 2 generations and 3 sibships, related through females, Chaganti and German (1979) observed infertility. Testicular tissue from the propositus showed desynapsis, lack of chiasmata and degeneration of spermatocytes during the first meiotic division. X-linked recessive and male-limited autosomal dominant inheritance were considered possibilities. (See 258150 for evidence of an autosomal recessive defect.) 'Bare patches' (Bpa) in mice is a semidominant X-linked trait associated with high frequency of XO females.

Molecular Genetics

By genomewide microarray analysis on DNA from 15 unrelated men of European descent with azoospermia, Yatsenko et al. (2015) identified a 90-kb hemizygous loss encompassing part of the TEX11 gene on chromosome Xq13.1 (300311.0001) in a patient with mixed testicular atrophy. Analysis of TEX11 in 48 additional azoospermic men of European descent revealed 2 more TEX11 mutations: a missense mutation (M171V; 300311.0002) in a man with meiotic arrest, and the same deletion as in the first patient in another man with meiotic arrest. In addition, sequencing revealed that 4 (1.7%) of 240 German men with azoospermia had mutations in TEX11, including 1 missense mutation (A598T; 300311.0003) and 3 splice site mutations (see, e.g., 300311.0004). None of the mutations were found in 384 men with normal sperm concentrations, although 3 were present in heterozygosity in female carriers in the dbSNP database (frequency, 0.1-0.2%). Overall, TEX11 mutations were detected in 7 (2.4%) of 289 patients, including 5 (15%) of 33 men with meiotic arrest and in 2 (1%) of 193 men with mixed testicular atrophy. No mutations were identified in 63 azoospermic men with Sertoli cell-only syndrome (see 305700).