A possible association of a human tektin-t gene mutation (A229V) with isolated non-syndromic asthenozoospermia: case report.

Asthenozoospermia (AZS), characterized by grade A + B sperm motility (as in World Health Organization Guidelines) < or =50% or A <25% in fresh ejaculate, may exist as an isolated disorder, in combination with other sperm anomalies or as part of syndromic association. The majority of syndromic patients can be ascribed to mutations in dynein genes, while, to date, no genes have been described to be associated in humans with non-syndromic, isolated AZS. An interesting family of axonemal proteins, the tektins, has been recently identified in various mammals and they are thought to play a fundamental role in ciliary movement. Recently, the human tektin-t (or h-tekB1 or Tektin-2) gene has been cloned, showing specific expression in flagella of mature sperm. We report the screening of tektin-t gene in 90 isolated non-syndromic AZS patients. We found a heterozygous mutation (A229V) in one patient. Ultrastructural analysis showed anomalies in > or =80% of examined spermatozoa involving axoneme microtubules and mitochondria. Moreover, the viability and mitochondrial function of sperm were altered in the patient with the A229V mutation. This is the first description of human pathology linked to a tektin-family gene, since only murine models are available for these genes.

Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy.

CONTEXT: An explosive growth in Y chromosome long arm (Yq) microdeletion testing demand for male infertility occurred in the past few years. However, despite the progresses in the biology of this chromosome, a number of molecular and clinical concerns are not supported by definitive data. OBJECTIVE: The objective was to provide information on the type and prevalence of microdeletions in infertile males, indication for testing, genotype-phenotype correlation, sperm aneuploidies, and genetic counseling. DESIGN AND SETTING: We performed a prospective study from January 1996 to December 2005 in an academic clinic. PATIENTS: We studied 3073 consecutive infertile men, of which 625 were affected by nonobstructive azoospermia and 1372 were affected by severe oligozoospermia. Ninety-nine patients with microdeletions are described here. MAIN OUTCOME MEASURES: Yq microdeletions, seminal analysis, reproductive hormones, testicular cytology/histology, and sperm sex chromosomes aneuploidies were used as outcome measures. RESULTS: The prevalence of microdeletions was 3.2% in unselected infertile men, 8.3% in men with nonobstructive azoospermia, and 5.5% in men with severe oligozoospermia. Only 2 of 99 deletions were found in men with more than 2 million sperm/ml. No clinical data are useful to identify a priori patients with higher risk of Yq microdeletions. Most deletions are of the AZFc-b2/b4 subtype and are associated with variable spermatogenic phenotype, with sperm present in 72% of the cases. Complete AZFa and AZFb (P5/Proximal P1) deletions are associated with Sertoli cell-only syndrome and alterations in spermatocyte maturation, respectively, whereas partial deletions in these regions are associated with milder phenotype and frequent presence of sperm. Men with AZFc-b2/b4 deletions produce a higher percentage of sperm with nullisomy for the sex chromosomes and XY-disomy. CONCLUSIONS: This extensive clinical research expands the knowledge on genotype-phenotype relationships and confirms that the identification of Yq microdeletions has significant diagnostic and prognostic value, adding useful information for genetic counseling in these patients.

Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations.

OBJECTIVE: Androgens and a functioning androgen receptor (AR) are essential for development and maintenance of the male phenotype and spermatogenesis. Consistent with this, mutations in the AR gene cause a variety of defects related to androgen insensitivity, ranging from complete feminization to phenotypic males with infertility. The aim of his study was to analyse the prevalence of AR gene mutations in male infertility and to clarify the genotype-phenotype relation. DESIGN: Males with infertility were recruited consecutively at the Centre for Male Gamete Cryopreservation at the University of Padova from January 1996 to January 2005. PATIENTS: One thousand five hundred and seventeen men with < 10 million sperm/ml and 310 age-matched normozoospermic controls. METHODS: Screening for AR gene mutation was done by DHPLC and sequencing, and reproductive hormone concentrations were measured. RESULTS: We found 20 mutations in 26 of 1517 patients (1.7%) and no mutations in controls. A high number of mutations localized in exon 1 of the AR gene coding for the transactivation domain of the protein. Of 20 mutations, 7 represent novel mutations. With respect to men without AR mutations, subjects with AR mutations have lower ejaculate volume, higher testosterone levels, higher oestradiol levels, and higher androgen sensitivity index. However, the ranges for these variables were highly overlapping between men with and without AR gene mutations. Also clinical manifestations of AR mutations are not unique and 22 men had only spermatogenic impairment. CONCLUSIONS: AR gene mutations are quite frequent in unselected infertile men but no specific hormonal or clinical data could be used to preselect patients at risk of mutations.