Background: Clinical course variability in Duchenne muscular dystrophy (DMD) is partially explained by the mutation location in the DMD gene and variants in modifier genes. We assessed the effect of the SPP1, CD40, and LTBP4 genes and DMD mutation location on loss of ambulation (LoA). Methods: SNPs in SPP1-rs28357094, LTBP4-rs2303729, rs1131620, rs1051303, rs10880, and CD40-rs1883832 were genotyped, and their effect was assessed by survival and hierarchical cluster analysis. Results: Patients on glucocorticoid corticosteroid (GC) therapy experienced LoA one year later (p = 0.04). The modifying effect of SPP1 and CD40 variants, as well as LTBP4 haplotypes, was not observed using a log-rank test and multivariant Cox regression analysis. Cluster analysis revealed two subgroups with statistical trends in differences in age at LoA. Almost all patients in the cluster with later LoA had the protective IAAM LTBP4 haplotype and statistically significantly fewer CD40 genotypes with harmful T allele and “distal” DMD mutations. Conclusions: The modifying effect of SPP1, CD40, and LTBP4 was not replicated in Serbian patients, although our cohort was comparable in terms of its DMD mutation type distribution, SNP allele frequencies, and GC-positive effect with other European cohorts. Cluster analysis may be able to identify patient subgroups carrying a combination of the genetic variants that modify LoA.

Results of numerous studies gave contradictory conclusions when analysing associations between copy number variants (CNVs) within the azoospermia factor (AZF) locus of the Y chromosome and idiopathic male infertility. The aim of this study was to identify the presence and possible association of CNVs in the AZF region of Y chromosome with idiopathic male infertility in the Serbian population. Using the multiplex ligation‐dependent probe amplification technique, we were able to detect CNVs in 24 of 105 (22.86%) infertile men and in 11 of 112 (9.82%) fertile controls. The results of Fisher's exact test showed a statistically significant difference between cases and controls after merging g(reen)–r(ed)/g(reen)–r(ed) and b(lue)2/b(lue)3 partial deletions identified in the AZFc region (p = 0.024). At the same time, we observed a trend towards statistical significance for a deletion among gr/gr amplicons (p = 0.053). In addition to these, we identified a novel complex CNV involving inversion of r2/r3 amplicons, followed by b2/b3 duplication and b3/b4 deletion, respectively. Additional analyses on a larger study group would be necessary to draw meaningful conclusions about associations among CNVs that presented with higher frequency in the infertile men than the fertile controls.

No abstract