A study of reciprocal translocations and inversions detected by light microscopy with special reference to origin, segregation, and recurrent abnormalities

Abstract

We analyzed 448 independently ascertained reciprocal translocations and 220 inversions referred to our diagnostic laboratory. Twenty-eight percent of the translocations and 8.5% of the inversions arose de novo, the proportion being influenced by the method of ascertainment. It was highest, 47%, among translocations ascertained through an abnormal phenotype. With the exception of the 3:1 unbalanced segregants, the remainders were equally likely to have been paternally or maternally inherited. The segregation from balanced translocation and inversion carriers showed an equal number of offspring with a normal chromosome constitution and with a balanced rearrangement. The number of unbalanced segregants among the translocations was 2.7% where the proband was balanced, and 19.2% where the proband was unbalanced. There was only a single unbalanced inversion. A search for recurring translocations showed only the well documented t(11;22) to occur with unusual frequency in our series and those of others, and we concluded that the few other translocations that were seen on more than one occasion were likely to be identical by descent (IBD). Similarly the majority of the recurring inversions, with the exception of "common variants," seemed likely to be IBD. However, eight inversions recurred in our data and in most other series and may well be genuine independent rearrangements. A search of the known olfactory receptor (OR) loci and duplicons suggested that such sequences did not form an important contribution to the breakpoints of recurring rearrangements detected by light microscopy.

Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

“…In the majority of cases, both parents were heterozygous for the specific translocation and each contributed to the subsequent homozygous offspring. In most instances (cases [1][2][3][4][5]8), there was a consanguinous parental relationship with a familial translocation. These include three siblings (cases 1-3) each heterozygous for t (13;14).…”

“…Chiefly, with the exception of a single-unbalanced translocation (case 9), homozygosity was determined for reasons other than an identifiable pathology. Three cases (6)(7)(8) were ascertained during prenatal screening. 22,26,27 Case 7 represents the first published report of RBT homozygosity, with fetal t(14;21) homozygosity ascertained after diagnosis of paternal t(14;21) heterozygosity through family cytogenetic analyses because of an earlier child born with significant motor and mental abnormalities and abnormal karyotype.…”

“…7 Reciprocal translocations involve exchanges between non-homologous chromosomes of any form, and while as a group are more common than non-homologous RBTs, with the exception of the well-recognized t(11;22)(q23;q11) translocation, the majority are assumed to be unique. 8 Chromosomal inversions arise from an intrachromosomal break and subsequent intrachromosomal rearrangement, and may be divided into pericentric and paracentric forms based on the position of the breakpoints relative to the centromere. [9][10][11][12] The majority of all inversions (66%) are of pericentric type.…”

“…15 Approximately 90% of all non-homologous RBTs and reciprocal translocations are balanced, with the estimated prevalence of balanced chromosomal inversions even higher. 3,8,[16][17][18] Studies suggest that the majority of constitutional rearrangements are inherited; B60% of non-homologous RBTs; between 65 and 75% of reciprocal translocations and over 90% of inversions. 2,8,[16][17][18] Although the familial transmission of such rearrangements across generations is well reported, reports of homozygosity are relatively rare, although include examples of all three forms.…”

“…3,8,[16][17][18] Studies suggest that the majority of constitutional rearrangements are inherited; B60% of non-homologous RBTs; between 65 and 75% of reciprocal translocations and over 90% of inversions. 2,8,[16][17][18] Although the familial transmission of such rearrangements across generations is well reported, reports of homozygosity are relatively rare, although include examples of all three forms. [19][20][21] Most data are in the form of individual case reports with description of ascertainment and any associated phenotypic abnormalities, for which great variation exists for individual homozygosities.…”