Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by dystonia, parkinsonism, cognitive and visual impairment, and iron accumulation in the brain. Many cases of PKAN result from mutations in the PANK2 gene that encodes pantothenate kinase 2, a key regulatory enzyme in the biosynthesis of coenzyme A. We previously detected six Serbian patients with clinically suggestive PKAN, all of whom had PANK2 c.1583C>T (p.T528M) mutation either in the homozygous or in the heterozygous state. In this study we explored the phenotypic expression and a possible founder effect of this substitution. We performed the analysis of linkage disequilibrium (LD) and organization in haplotypes of 23 single nucleotide polymorphisms (SNPs) adjacent to the PANK2 gene in all of the six patients and their parents, as well as in control healthy child-parents trios. The age of PANK2 c.1583C>T mutation was determined using the r 2 degeneration method. Clinical findings in our patients were markedly similar. Different LD structures between patients and controls is revealed, and PANK2 c.1583T allele was significantly associated with a particular haplotype. The age of PANK2 c.1583C>T mutation was estimated to be about 15 generations. Our results suggest that PANK2 c.1583C>T in Serbian PKAN patients represents a founder mutation descended from one common ancestor.

This paper presents a case of a sixteen-year-old female patient with agenesis of corpus callosum which was accidentally discovered during etiological investigation of the consciousness disorder. Agenesis of corpus callosum, a rare congenital defect, might be associated with macrocephalia and various degrees of mental impairment, optic defects, and seizures. Apart from patients with these pathologic states, there are individuals with agenesis of corpus callosum, but without any clinical disturbances.

Background/Aim. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. They are X-linked recessive diseases, where males are affected and females are mostly healthy carriers of the mutation. It is estimated that 2/3 mothers of DMD probands are carriers, while 1/3 of patients have de novo mutations. The aim was to confirm the carrier status of females in the families of DMD/BMD probands, using direct genetic methods. Methods. We tested 38 females from 31 families of DMD/BMD probands with deletion/duplication in the dystrophin gene. Also, 4 cases of prenatal diagnosis of DMD/BMD were included. We preformed the polymerase chain reaction (PCR) and the multiplex ligation-dependent method (MLPA) for deletion detection, i.e. deletion/duplication in the dystrophin gene. Results. In 31 DMD/BMD probands, we identified 87.1% deletions and 12.9% duplications of one or more exons. Of the 29 tested mothers, mutations were found in 17 (14 deletions and 3 duplications). Mutations were found in 57.9% (11/19) mothers of DMD and in 60% (6/10) mothers of BMD, respectively. Also, in probands with deletions 56% (14/25) of mothers were carries and in probands with duplications 3 mothers of 4 (75%). Of the 9 other female relatives, mutations were found in 4. In prenatal diagnosis, we identified deletion in one male and one female foetus of one mother. Conclusion. The study showed that mothers were carriers in almost 60% of sporadic cases of DMD/BMD with deletions and duplication. Also, the carrier frequency tended to be higher in mothers of the probands with duplication (75%) then in probands with deletions (56%). In the case of a mother who was confirmed as a carrier, deletion was detected in 2 of 3 foetuses.

Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by progressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystrophinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) methods, according to the protocol, to detect or confirm mutations in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44-60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod domain. An exception to Monaco's rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband's mothers were confirmed as carriers.