Der(22)t(11;22) resulting from a paternal de novo translocation, adjacent 1 segregation, and maternal heterodisomy of chromosome 22.

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...

Small Supernumerary Marker Chromosomes and Uniparental Disomy Have a Story to Tell

“…For complex sSMC , only one patient with maternal heterodisomy of chromosome 22 has been reported to date in Emanuel syndrome cases (Dawson et al 1996).…”

Trisomy First, Translocation Second, Uniparental Disomy and Partial Trisomy Third: A New Mechanism for Complex Chromosomal Aneuploidy

“…She had neonatal diabetes and low birth weight, but no other anomalies and, up to the age at report, developed normally. Dawson et al [16] reported a patient with partial trisomy 1 lq and 22 due to a de novo extra 11 ;22 translocation chromosome. This is the first…”

A unique case of der(11)t(11;22),-22 arising from 3:1 segregation of a maternal t(11;22) in a family with co-segregation of the translocation and breast cancer

“…The single example with a 46,XX,der(22) karyotype, with monosomy for 22q and trisomy for 11q, was found in an early embryonic death resulting in an empty sac (Soler et al, 1993). The other cases produced viable offspring due to subsequent events that rescued the monosomy 22: in one case through a maternal MI nondisjunction of 22 (Dawson et al, 1996), and, in others, most probably by postzygotic nondisjunction involving the der (22) chromosome (Kulharya et al, 2002). Five cases with karyotype 47,t(11;22),+der(22) and phenotype similar to the usual der(22) have been reported (Lockwood et al, 1989;Abeliovich and Carmi, 1990;Lurie and Podelschuk, 1992;Simi et al, 1992;Petkovic et al,1996).…”

“…der (22) syndrome Dawson et al (1996) 47,XX/XY,t(11;22)(q23;q11.2)pat, +der (22) ? 2 : 2 alternate + MII or postzygotic nondisjunction of der (22) der (22) Petkovic et al (1996) 46,XX,der (22) …”