Familial complex chromosome rearrangement ascertained by in situ hybridisation.

Abstract

A complex familial chromosome translocation has been ascertained by combining classical cytogenetics and CISS (chromosomal in situ suppression). Cytogenetic analysis of a chorionic villus sample with G banding showed a 47,XX,-2, +der(2)t(2;22),+der(22)t(2;22) karyotype. Analysis of peripheral blood lymphocytes from the parents by G banding and CISS showed a more complex translocation in the father: 46,XY,-2,-11,-22, +der(2) t(2;11)(q13;q23), +der(11) t(11;22) (q23; qI1.2), +der(22) t(2;22) (ql3;ql1.2).Definitive analysis of cultured amniotic fluid cells showed a double partial trisomy of chromosomes 11 and 22. The couple decided to continue the pregnancy. The fetal karyotype was confirmed at birth. Clinical abnormalities present in our patient were typical of an unbalanced 11;22 translocation. Our findings confirm that chromosome painting techniques allow a better characterisation of complex chromosome rearrangements which may be difficult to detect in G banded karyotypes.

Sperm segregation analysis of a complex chromosome rearrangement, 2;22;11, by whole chromosome painting

“…These children are trisomic for the centric segment of chromosome 22 (22pter → q11) and for the distal portion of chromosome 11 (11q23→ qter) and result from the 3:1 segregation of the two normal chromosomes 11 and 22 and the der(22). In the family studied by us, the affected daughter was also trisomic for these same segments and had the characteristic phenotype of the unbalanced children born to carriers of the common t(11;22), but in our case the child resulted from a 4:2 segregation of the hexavalent (Fuster et al, 1997).…”

“…Characterization of the sperm segregation products has been done by whole chromosome painting, thus allowing simple, reliable identification of the normal and the derivative chromosomes. Although CCR has been considered extremely infrequent, the re-evaluation of previous cases using FISH has resulted in the identification of an increasing number of CCRs (Smart et al, 1989, Hertz et al, 1993, Ohta et al, 1993, Fuster et al, 1997. Thus, a combination of classical and molecular cytogenetic techniques must be used for the proper characterization of chromosome abnormalities (see Fuster et al, 1997).…”

“…1) was ascertained after the birth of a daughter with a 47,XX,-2, +der(2)t(2;11) (q13;q23),+der(22)t(2;22)(q13;q11.2) karyotype (Fuster et al, 1997). His wife had previously had three spontaneous abortions and a phenotypically and chromosomally normal son (Fig.…”

FISH analysis of a complex chromosome rearrangement involving nine breakpoints on chromosomes 6, 12, 14 and 16

“…CCRs result when three or more independent breaks occur in two or more chromosomes and the broken segments rejoin at random to form various derivative chromosomes (Fuster et al, 1997). Review of the literature reveals rearrangements involving from 2 to 7 chromosomes and from 3 to 10 breakpoints (Kousseff et al, 1987;Tupler et al, 1992).…”

Molecular cytogenetic characterisation of a complex 46,XY,t(7;8;11;13) chromosome rearrangement in a patient with Moebius syndrome

“…However, in some instances, for example, subtelomeric24 and other cytogenetically cryptic rearrangements4 25 or CCRs,7 13 chromosome banding techniques alone may not allow an exact karyotype interpretation and correlation between genotype and phenotype. This is why FISH has become an important accessory technique in clinical cytogenetics.…”