Spermatogenic Failure, X-Linked, 1

Description

In the evaluation of male infertility, the Sertoli cell-only (SCO) syndrome is diagnosed on testicular biopsy when either no germ cells are visible in any seminiferous tubules (SCO type I) or germ cells are present in a minority of tubules (SCO type II). It is believed that the latter variant arises from a failure to complete differentiation and maturation of spermatocytes and spermatids, leading to degeneration of germ cells within most tubules (Sargent et al., 1999).

There is evidence that Sertoli cell-only syndrome can be caused by interstitial deletions in the 'azoospermia factor' (AZF) region on the long arm of the Y chromosome (SPGFY1; 400042).

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

Edwards and Bannerman (1971) observed 2 brothers, aged 14 and 12, with gynecomastia and obesity. Their disorder might have been classified simply as adolescent or pubertal gynecomastia were it not for the existence of 2 maternal uncles with a history of pubertal gynecomastia and, in the one of them available for study, clinical features and testicular biopsy consistent with the Del Castillo syndrome. By the age of 26, he showed no gynecomastia. In the 14-year-old nephew, the sperm count was probably low but sperm were present. The authors suggested that in this boy they had an opportunity to observe the Del Castillo syndrome at an earlier stage than had previously been possible. They suggested that, as in other similar conditions such as the testicular feminization syndrome (300068) and the Reifenstein syndrome (312300), the inheritance is either X-linked or male-limited autosomal dominant. Several kindreds with multiple affected males are known.

Chaganti et al. (1980) suggested that the pathology may be similar to that in the mouse mutations 'white' (W) and 'steel' (SL), autosomal recessive disorders in which primordial germ cells fail to multiply and adult testes lack germ cells. Both males and females are sterile.

The USP26 gene (300309), which is specifically expressed in testis tissue, has been studied as a potential infertility gene. In 8 of 111 patients (7.2%) with Sertoli cell-only syndrome, Stouffs et al. (2005) found the same 3 changes in the nucleotide sequence of the USP26 gene, all on the same allele: an insertion, 370-371insACA, and 2 transitions, 494T-C and 1423C-T. These changes were not found in 152 fertile controls or 32 patients with azoospermia with maturation arrest (270960). Stouffs et al. (2005) suggested that these changes might be involved in male infertility or increase the risk of male infertility.

Stouffs et al. (2006) analyzed 146 Caucasian patients with cryptozoospermia or oligozoospermia and 202 controls and identified the USP26 haplotype only in 1 control individual who had normal spermatogenesis on testicular biopsy. Stouffs et al. (2006) concluded that the previously identified cluster of changes does not affect spermatogenesis per se.

Ravel et al. (2006) demonstrated that 2 of the changes identified by Stouffs et al. (2005) in the USP26 gene, 494T-C and 370insACA, correspond to the ancestral sequence of the gene, and that the USP26 haplotype is present in significant frequencies in sub-Saharan African and South and East Asian populations, including individuals with known fertility. Ravel et al. (2006) concluded that the allele is not associated with infertility.