title: Combinations of genetic changes in the human cAMP-responsive element modulator gene: a clue towards understanding some forms of male infertility?
abstract: The cAMP-responsive element modulator (CREM) gene plays a pivotal role in the mouse spermatogenesis, but its role in the human infertility has not been fully established. We performed a mutation screening in 13 Slovenian men with round spermatid arrest and in six controls. Eleven genetic changes have been identified in the human CREM gene, three novel single-nucleotide polymorphisms [within the promoters P1, P3 and intervening sequence 1 (IVS1)], one insertion (IVS2) and one non-sense mutation (exon gamma). Some infertile patients seem to accumulate potentially harmful genetic changes. We identified a patient with no CREM immunoreactive protein that was homozygous for the nucleotide changes in all promoters, IVS 1, 2, 6, and was heterozygous for the mutation in exon gamma. Interestingly, insertion in IVS2 (IVS2-58_55insT) results in a four-fold decrease in binding of nuclear proteins. Computer predictions suggested the presence of a potential novel CREM promoter, however, random amplification of cDNA ends from the human testis cDNA library was not successful in confirming a novel transcription start site of the CREM gene. Screening of a larger number of patients and controls is required to elucidate whether the observed combinations of genetic changes in the CREM gene can explain some forms of male infertility.
authors.affiliation: Institute of Biochemistry, Medical, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: K
authors.initials: K
authors.lastname: Vouk
authors.forename: P
authors.initials: P
authors.lastname: Hudler
authors.forename: L
authors.initials: L
authors.lastname: Strmsnik
authors.forename: M
authors.initials: M
authors.lastname: Fink
authors.forename: G
authors.initials: G
authors.lastname: Majdic
authors.forename: B
authors.initials: B
authors.lastname: Zorn
authors.forename: E
authors.initials: E
authors.lastname: Lalli
authors.forename: P
authors.initials: P
authors.lastname: Sassone-Corsi
authors.forename: N
authors.initials: N
authors.lastname: Debeljak
authors.forename: R
authors.initials: R
authors.lastname: Komel
authors.forename: D
authors.initials: D
authors.lastname: Rozman
mesh_terms: D000328:Adult; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial; D000242:Cyclic AMP / Q000502:physiology*; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics* / Q000378:metabolism; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020218:Response Elements / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013737:Testis / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP