• PMID: 11756355
• Gene Name: DAZ1
• Condition: Infertility
• Association: The genetic risk factors identified in this study were abnormal karyotypes, DAZ gene deletion in AZFc region, CFTR gene mutaions, Y chromosomal microdeletions, sex- chromosomal aneuploidy and 6 translocations
• Mutation: Sex-chromosomal aneuploidy, translocations, Y chromosomal microdeletions
• Population size: 150
• Population details: 150 infertile
• Sex: Male
• Infertility type: Male infertility
• Associated genes: AZF, CFTR
• Other associated phenotypes: Azoospermia, Oligozoospermia

Genetic risk factors in infertile men with severe oligozoospermia and azoospermia

Dohle GR, Halley DJ, Van Hemel JO, van den Ouwel AM, Pieters MH, Weber RF, Govaerts LC.

BACKGROUND: Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors. METHODS: In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome abnormalities, microdeletions of the Y chromosome (AZF region) and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. RESULTS: Genetic analysis identified 16/150 (10.6%) abnormal karyotypes, 8/150 (5.3%) AZFc deletions and 14/150 (9.3%) CFTR gene mutations. An abnormal karyotype was found both in men with oligozoospermia and azoospermia: 9 men had a sex-chromosomal aneuploidy, 6 translocations were identified and one marker chromosome was found. Y chromosomal microdeletions were mainly associated with male infertility, due to testicular insufficiency. All deletions identified comprised the AZFc region, containing the Deleted in Azoospermia (DAZ) gene. CFTR gene mutations were commonly seen in men with congenital absence of the vas deferens, but also in 16% of men with azoospermia without any apparent abnormality of the vas deferens. CONCLUSIONS: A genetic abnormality was identified in 36/150 (24%) men with extreme oligozoospermia and azoospermia. Application of ICSI in these couples can result in offspring with an enhanced risk of unbalanced chromosome complement, male infertility due to the transmission of a Y-chromosomal microdeletion, and cystic fibrosis if both partners are CFTR gene mutation carriers. Genetic testing and counselling is clearly indicated for these couples before ICSI is considered. FAU - Dohle, G R AU - Dohle GR AD - Andrology Unit, Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Dohle@urol.azr.nl FAU - Halley, D J J AU - Halley DJ FAU - Van Hemel, J O AU - Van Hemel JO FAU - van den Ouwel, A M W AU - van den Ouwel AM FAU - Pieters, M H E C AU - Pieters MH FAU - Weber, R F A AU - Weber RF