Familial translocation between chromosomes 3 and 10: meiotic segregation, diagnostics and clinical features of...

Reciprocal translocations are the most common structural chromosomal rearrangements, occurring at a frequency of 0.08-0.3 % in the human population. The vast majority of carriers of reciprocal translocations are phenotypically normal, but have an increased risk of miscarriage or the birth of children with intellectual disabilities and multiple congenital abnormalities due to meiotic malsegregation of chromosomes involved in the translocation. This study presents a familial case of translocation involving the distal regions of the short arms of chromosomes 3 and 10, detected in seven family members across three generations. The investigation was prompted by the detection of a deletion 10p15 and a duplication 3p25 revealed through clinical exome sequencing in a proband exhibiting phenotypic abnormalities, which may correspond to der(10)t(3;10)(p25;p15). GTG cytogenetic study of the proband's family revealed that the mother, grandmother, aunt and brother - none of whom displayed any clinical or phenotypic manifestations - were carriers of a balanced chromosomal rearrangement, t(3;10)(p25;p15). By contrast, the karyotype of the proband's sibling - a girl with severe cognitive, neurological, and developmental abnormalities - was found to be 46,XX,der(3)t(3;10)(p25;p15)dmat. Molecular karyotyping facilitated further clarification of the chromosomal imbalance and the precise breakpoints on both chromosomes involved in the translocation. This study provides a detailed description of the clinical and phenotypic manifestations resulting from the presence of derivative chromosomes 3 and 10 in the karyotype. Additionally, it discusses the mechanisms underlying the formation of chromosomal imbalances in the family members with the abnormal phenotype, the relationship between the severity of clinical manifestations and changes in gene dosage due to chromosomal rearrangements, as well as potential preventive and rehabilitative measures aimed at reducing the risk of chromosomal pathology in the families with carriers of autosomal reciprocal translocations.