Road to A Rare Diagnosis: A Case Report Exploring Phenotype, Clinical Management and Outcome of a Rare and Novel Unbalanced Translocation causing complete Trisomy 17p

Background: Trisomy 17 is a rare chromosomal disorder with limited existing literature that mostly refer to mosaic Trisomy 17 cases. Our report summarizes the clinical course of a neonate with a Trisomy 17 karyotype der (14;17) (q10; p10), + 17 pat. Key words: Trisomy 17, Unbalanced translocation, Paternal origin

Evaluation of Bulls and Related Groups of the Jersey Breed on Dairy Productivity and Reproductive Capacity of Offspring

The article presents the results of research on the influence of paternal origin and belonging to a related group on the level of milk productivity of cows and the reproductive capacity of Jersey cows in the farm “Dan-Milk” of the Zhytomyr Region. The purpose of this study is to establish the influence of paternal origin and belonging to a related group on the level of milk productivity and reproductive capacity parameters of Jersey cows. The study established a substantial level of differentiation in the main economically useful features between groups of half-sisters by father. The best quantitative indicators of milk productivity were noted among the daughters of bulls DJ Jante 302761 (P<0.001) and Headline 114114336 (P<0.001), the worst indicators – among daughters of Karl 67037285. The highest indicators of fat and protein content in milk were noted in the cows bred from the bull Legal 61929249, the lowest – from the bull Karl 67037285. The influence of the origin of cows by father on the variability of milk yield and yield of milk fat and protein was 20.3–30.3% (up to P<0.001), the content of fat and protein in milk decreased to 13.2-20.0% (P<0.01 and P<0.05), and according to the reproductive capacity features – to 7.8-19.0% with an unreliable level of statistical significance. Prepotent as to milk yield are bulls Legal 61929249 and Headline 114114336, as to the content and yield of milk protein – Legal 61929249. Cows of the related group bred from the bull Observer 553236 are characterised by the highest milk yield and yield of milk fat and protein for both the first and best lactation, and cows of the related group bred from Surville 604694 are characterised by the worst yield. The influence of belonging to a related group on the studied features was several times lower (0.2-10.5%) compared to the influence of paternal origin. With an increase in the milk yield of cows over the first lactation, there is a stable and substantial decrease in the reproductive capacity coefficient due to the lengthening of the service period between the first and second calving. Such natural antagonism does not imply the goal of increasing the duration of the service period to obtain maximum milk yields for firstborn cows, since this will lead to a decrease in the yield of calves and render timely replenishment of the herd impossible. It is optimal to milk the firstborn up to 8 tonnes over 305 days of lactation while maintaining a satisfactory reproductive level

Parthenogenetic mosaicism: generation via second polar body retention and unmasking of a likely causative PER2 variant for hypersomnia

Background Parthenogenetic mosaicism is an extremely rare condition identified only in five subjects to date. The previous studies indicate that this condition is mediated by parthenogenetic activation and is free from a specific phenotype ascribed to unmaking of a maternally inherited recessive variant in the parthenogenetic cell lineage. Results We examined a 28-year-old Japanese 46,XX female with Silver-Russell syndrome and idiopathic hypersomnia. The results revealed (1) predominance of maternally derived alleles for all the differentially methylated regions examined; (2) no disease-related copy-number variant; (3) two types of regions for all chromosomes, i.e., four BAF (B-allele frequency) band regions with single major microsatellite peaks of maternal origin and single minor microsatellite peaks of non-maternal (paternal) origin, and six BAF band regions with single major microsatellite peaks of maternal origin and two minor microsatellite peaks of maternal and non-maternal (paternal) origin; (4) an unmasked extremely rare PER2 variant (c.1403G>A:p.(Arg468Gln)) with high predicted pathogenicity; (5) mildly affected local structure with altered hydrogen bonds of the p.Arg468Gln-PER2 protein; and (6) nucleus-dominant subcellular distribution of the p.Arg468Gln-PER2 protein. Conclusions The above findings imply that the second polar body retention occurred around fertilization, resulting in the generation of the parthenogenetic cell lineage by endoreplication of a female pronucleus and the normal cell lineage by fusion of male and female pronuclei, and that the homozygous PER2 variant in the parthenogenetic cells is the likely causative factor for idiopathic hypersomnia.

Preferentially Paternal Origin of De Novo 11p13 Chromosome Deletions Revealed in Patients with Congenital Aniridia and WAGR Syndrome

The frequency of pathogenic large chromosome rearrangements detected in patients with different Mendelian diseases is truly diverse and can be remarkably high. Chromosome breaks could arise through different known mechanisms. Congenital PAX6-associated aniridia is a hereditary eye disorder caused by mutations or chromosome rearrangements involving the PAX6 gene. In our recent study, we identified 11p13 chromosome deletions in 30 out of 91 probands with congenital aniridia or WAGR syndrome (characterized by Wilms’ tumor, Aniridia, and Genitourinary abnormalities as well as mental Retardation). The loss of heterozygosity analysis (LOH) was performed in 10 families with de novo chromosome deletion in proband. In 7 out of 8 informative families, the analysis revealed that deletions occurred at the paternal allele. If paternal origin is not random, chromosome breaks could arise either (i) during spermiogenesis, which is possible due to specific male chromatin epigenetic program and its vulnerability to the breakage-causing factors, or (ii) in early zygotes at a time when chromosomes transmitted from different parents still carry epigenetic marks of the origin, which is also possible due to diverse and asymmetric epigenetic reprogramming occurring in male and female pronuclei. Some new data is needed to make a well-considered conclusion on the reasons for preferential paternal origin of 11p13 deletions.