Inverted duplication syndrome with an adjacent terminal deletion of the short arm of chromosome 8—inv dup del(8p)—is a rare complex structural chromosomal rearrangement with a wide range of clinical manifestations. Molecular cytogenetic variants of chromosomal imbalance depend on the mechanism of rearrangement formation. We analyzed the clinical–genetic and molecular cytogenetic characteristics of the 8p inverted duplication/deletion syndrome, as well as the genotype–phenotype correlation in eight unrelated cases with the rearrangement of inv dup del(8p). The main clinical manifestations in all cases are psychomotor and language delay, muscle hypotonia, and dysmorphic facial features. Malformations of the central nervous system, such as corpus callosum agenesis, were found in five cases. Seizures were reported in only one case. We found that the cause of the formation of the rearrangement was generally ectopic recombination (seven out of eight cases) and this was due to U-type exchange in only one case. Depending on the mechanism of formation, the characteristics of the genomic imbalance were different, which made it possible to identify two molecular cytogenetic variants in the cases we describe here. No association between molecular cytogenetic variants and clinical manifestations was found.

One of the causes of spontaneous pregnancy termination, infertility, and birth of children with development delay and malformations are chromosomal abnormalities (CA) as well as spontaneous aneuploidies in gametes of phenotypically normal parents. Often couples with reproductive problems, as well as spouses one of whom is a carrier of CA, turn to the programs of assisted reproductive technologies (ART) for preimplantation evaluation of the zygote chromosomal status. As part of ART programs, parental gametes are examined to assess the level of spontaneous aneuploidy. As a rule, the most accessible material for analysis is the ejaculate. Fluorescent in situ hybridization (FISH) is used to examine male gametes obtained from the ejaculate. However, this FISH-analysis has a number of limitations and difficulties because of the peculiarities of the sperm head structure, namely the supercondensed state of chromosome chromatin. In order to optimize the FISH protocol, five different protocols were used for pre-hybridization processing of ejaculate samples obtained from nine phenotypically normal men. A comparative analysis of hybridization efficiency showed that the protocol using tris(2-carboxyethyl)phosphine hydrochloride (TCEP) as a decondensation agent was the most effective for subsequent molecular cytogenetic studies. The developed hybrid protocol combining proteolytic pretreatment, TCEP and thermal decondensation can be used when other protocols for pre-hybridization treatment of ejaculate preparations are not effective.

2q37 deletion syndrome is characterized by terminal deletions of the long arm of chromosome 2 and a variable clinical picture that includes type E brachydactyly, obesity, delayed motor and psychomotor development, congenital malformations of internal organs and the facial phenotype particular qualities. Authors present the two clinical case reports of patients with 2q37 deletions demonstrating different clinical manifestations. Proband 1 complained exclusively of brachydactyly while proband 2 had almost the full spectrum of clinical symptoms characterizing the syndrome. The Face2Gene AI-Powered Diagnosis & Care Management Tool suggested the correct diagnosis in both cases based on the features of the facial phenotype that in its turn became the key factors in choosing the tactics for further molecular genetic diagnostics. Conclusion: careful collection of anamnesis data, description of the facial phenotype and the use of artificial intelligence-based tools can become the key factors in choosing the tactics for the molecular genetic diagnostics available for practitioners of various specialties.

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be identified unambiguously by standard cytogenetic methods. A comprehensive approach involving the use of molecular cytogenetic methods is required for the more thorough morphological assessment of such chromosomes, as well as for the development of strategy for genetic counseling of the patients being the sSMC carriers. It is widely accepted that the development of abnormal phenotype by the patients having sSMC in their karyotype is associated with the presence of euchromatic region material in the marker chromosome. Therefore, it results from the presence of relatively large DNA copy number variations (CNVs) in the form of duplication, triplication, and more increased copy numbers; which are localized in the pericentromeric region of the appropriate chromosome. Pericentromeric CNVs can be involved in the chromosome imbalance in asymptomatic carriers of sSMC as well, however, the boundaries of such imbalance have not been clearly identified. The study was aimed to acquire additional information about the genomic topology of the DNA regions insensitive to the genes copy number increase. FISH analysis with commercial and homemade DNA probes was performed in 18 carriers of sSMC 15 and 22 having no clinically significant phenotypic abnormalities. The molecular cytogenetic testing showed that pericentromeric euchromatic regions sized 1.2 Mb and 714 kb, respectively, were found in 33% of cases (6 out of 18). We assume that these regions comprise no potentially dosage-sensitive genes.

A paracentric inversion (PAI) is a rare type of balanced intrachromosomal structural rearrangement. Heterozygotes for PAI are usually phenotypically normal, but the presence of the inversion may occasionally lead to synapsis and recombination disruptions during meiosis. PAI can be responsible for the production of recombinant chromosomes and unbalanced gametes. The risks associated with the birth of a child with chromosomal imbalances due to the generation of unbalanced crossover gametes is considered to be low. Nonetheless, viable offspring with intellectual disabilities and/or congenital abnormalities, as well as early miscarriages, stillbirth and infertility in heterozygous carriers of PAI have been described. Paracentric inversions may arise on various chromosomes. PAI with breakpoints on the long arm of chromosome 7 is among the most prevalent ones in humans. To assess the meiotic behavior of abnormal chromosome 7, as well as the empirical risk of producing gametes with recombinant chromosomes, the sperm FISH analysis of a male heterozygous carrier of inv(7)(q11.23q22) was performed. The percentage of recombinant sperms was 0.7 % and chromosomal imbalance was represented as reciprocal breakage products of a dicentric chromosome 7. Notably, spermatozoa with a dicentric chromosome 7 were not observed, which confirms its instability during meiosis I. Meiotic segregation analysis in the heterozygous carrier of inv(7)(q11.23q22) revealed a predominant formation of gametes containing either the inverted or the intact chromosome 7, occurring at frequencies of 52.2 and 47.8 %, respectively. This report is the first study providing a detailed description of meiotic segregation patterns of inv(7)(q11.23q22) by using a sperm FISH approach. Recombinant gamete formation confirms the occurrence of crossing-over within the inversion loop. Consequently, the individual risk of generating gametes (and subsequent zygotes) with chromosome 7 imbalance for this heterozygous carrier remains low.