No abstract

The t(11;22)(q23;qll) translocation is the most frequently identified familial reciprocal translocation in humans. In translocation carriers, 3:1 meiotic segregation with tertiary trisomy can occur resulting in abnormal progeny with the der(22) as the supernumary chromosome. Affected children have a distinct phenotype with multiple anomalies and severe mental retardation. We have identified a child with developmental delay and multiple anomalies consistent with the der(22) phenotype. Cytogenetic analysis showed an abnormal chromosome complement of 47,XX, +der(22)t(11;22)(q23; qll) in all 50 cells analysed. FISH analysis using chromosome 11 and 22 painting probes showed a pattern consistent with a reciprocal translocation of the distal bands 11q23 and 22qll respectively. Parental karyotypes were normal. RFLP analysis of locus D22S43, which maps above the t(11;22) breakpoint, showed that the der(22) was paternal in origin and indicated that the normal chromosomes 22 were the probable result of maternal heterodisomy. RFLP analysis of locus D22S94, which maps below the t(11;22) breakpoint, also suggested that both normal chromosomes 22 of the child represented the two maternal homologues. Non-paternity was excluded through the analysis of 10 microsatellite markers distributed on 10 different chromosomes and three VNTRs on three different chromosomes. To the best of our knowledge, this is the first reported case of a patient with an abnormal karyotype resulting from a de novo translocation in the paternal germline with probable unbalanced adjacent 1 segregation and maternal non-disjunction of chromosome 22 in meiosis I. (JT Med Genet 1996;33:952-956) Key words: der (22) A balanced carrier for this translocation does produce other types of unbalanced gametes.45 Analysis of the sperm chromosome complements of balanced carriers showed that all forms of 2:2 segregants, including alternate and adjacent 1 and 2, as well as 3:1 segregants, are produced. This indicates that adjacent 1 and 2 segregants are formed but lead to non-viable conceptuses. There are no reports of viable offspring resulting from adjacent 1 and 2 meiotic segregation in a heterozygote for this translocation.There have been several reported cases of abnormal offspring having inherited both the parental balanced translocation as well as the der (22) as a supernumary chromosome.69 These cases, it has been suggested, are the result of alternate segregation at meiosis I with either meiotic II or postzygotic non-disjunction ofthe der(22) which, in addition to the presence of the two translocated chromosomes, has resulted in a 47,XX/XY,t(11;22) (q23.3;q 1.2), + der(22)t(11;22)(q23.3;ql 1.2) karyotype. This karyotype has also been postulated to result from a crossover involving the normal chromosome 22 and the der(22) between the centromere and translocation breakpoint, followed by 3:1 segregation of the der(11), der (22) Chromosomes studies were performed on lymphocytes using standard methods."1 Fluorescent in situ hybridisation (FISH) was performed...

The regions near telomeres of human chromosomes are gene rich. Chromosome subtelomere rearrangements occur with a frequency of 7–10% in children with mild‐to‐moderate mental retardation (MR) and approximately 50% of cases are familial. Clinical investigation of subtelomere rearrangements is now prompted by fluorescence in situ hybridization (FISH) analysis using specific DNA probes from all relevant chromosome ends. In our study, 40 children were selected for subtelomere assay using either the Chromophore Multiprobe‐T Cytocell device or the VYSIS TelVision probes. Inclusion criteria were: developmental delay or MR; a normal 550 G‐band karyotype; FRAXA negative; and at least one other clinical criterion. Exclusion criteria included an identified genetic or environmental diagnosis. Of the 40 patients analysed, four (10%) were found to have subtelomere rearrangements. Three of 40 (7.5%) were found to have an unbalanced subtelomere rearrangement and one of 40 (2.5%) was found to have an apparently normal variant subtelomere deletion. The first of the three with an unbalanced karyotype was the result of a familial translocation, the second was a de novo finding, and the origin of the third could not be determined. The subtelomere FISH assay detected almost twice the frequency of unbalanced karyotypes as those detected by 550 G‐banding in our cytogenetics laboratory (4.7%). In addition, subtelomere screening was eight times more likely than fragile X screening in our DNA laboratory (1%) to detect genetic abnormalities in mentally handicapped individuals. Our findings support the view that screening for subtelomere rearrangements has a greater positive yield than other commonly used genetic investigations and, if cost and resources permit, should be the next diagnostic test of choice in a child with unexplained MR/dysmorphisms and a normal 550 G‐band karyotype.

of microarray and conventional cytogenetics would allow for more sensitive, comprehensive, and accurate analysis of the underlying genetic profile, with concomitant improvement in prognosis and treatment, not only for pediatric all, but for neoplastic disorders in general.