[Diagnosis of fragile X syndrome]. / Diagnostico del síndrome X frágil.

The fragile X syndrome (FXS) is the main cause of hereditary mental retardation. Although a lower frequency has been demonstrated in latest population studies, FXS constitutes the most frequent cause of hereditary mental retardation. FXS was historically diagnosed, firstly, only in clinically affected patients, but it was not possible to detect carriers with no symptoms. Once the mechanisms that specifically induced X chromosomal fragility were beginning to be understood, it became possible to confirm clinically diagnosed patients and detect some of asymptomatic carriers. But, the discovery of FMR1 gene has allowed us to reliable know the genetic status of anyone with respect to fragile X syndrome, independently of whether one belongs to a fragile X family. In this respect a combination of molecular and cytogenetic techniques may be used to detect expansions in the repeat region of the FMR1 gene. Three classes of alleles are found, normal with 5-60 repeats, premutated with repeats between 60 and 200 copies and full mutated with expansion greater than 200 copies.

Screening for AZF deletion in a large series of severely impaired spermatogenesis patients.

Recent investigations have pointed to a high prevalence of Y chromosome submicroscopic deletions in men with severely impaired spermatogenesis. We report on the incidence in 128 infertile men, in whom karyotype, sperm count, and hormonal parameters were evaluated. Patients with abnormal karyotype (other than an abnormal Y chromosome) or sperm concentration of more than 2 million/mL were excluded. Genomic DNA was extracted from the peripheral leukocytes of 57 men with azoospermia and 71 with severe oligospermia. Molecular analysis was performed by 3 multiplex polymerase chain reactions using a set of 9 sequence tagged sites (STSs) from 3 different regions of the Y chromosome: AZFa, AZFb, and AZFc. In 7% of the studied patients Yq microdeletions were detected, with a high prevalence in men with azoospermia (14%). No deletions were detected in the AZFa region. Deletions were present in AZFb, AZFc, or both regions. The deletion observed in 1 patient that did not overlap with the DAZ region demonstrates that genes other than DAZ may also be involved in the pathogenesis of some subsets of male infertility. Furthermore, common Yq deletions present different testicular pictures, suggesting that some unknown factors may be disturbing spermatogenesis. Because men with severe infertility suffer a high risk of Y chromosome deletion, screening for these men is recommended prior to treatment with assisted reproduction.

FRAXE mutation analysis in three Spanish families.

Very little is known about the phenotype of FRAXE-positive individuals and the relation between the genotype/phenotype and genotype/ cytogenetic expression. We describe three families with normal and mildly affected individuals and a severely retarded male expressing fragility at the FRAXE locus or presenting different expansions at the CGG FRAXE triplet. In addition, we analyze the FRAXE mutation in sperm DNA from a retarded male carrier with a handicapped daughter expressing fragility at the FRAXE locus. Mental status in FRAXE individuals is highly variable and, although mild mental retardation is observed in most cases, several carrier males are apparently normal. It seems that methylation is not as strictly associated with size of CGG triplets in the FRAXE locus as in FRAXA, and it is possible that normal carrier individuals with fully methylated increments in lymphocytes have a certain proportion of unmethylated alleles in the critical (i.e., neural) tissues, FRAXE mutation is apparently similar to FRAXA in that males with somatic large methylated increments are carriers of small unmethylated ones in germinal cells.