Recombinant balanced and unbalanced translocations as a consequence of a balanced complex chromosomal rearrangement involving eight breakpoints in four chromosomes

Abstract

We report on a family with a balanced complex chromosomal rearrangement (CCR) involving eight breakpoints between chromosomes 6, 7, 18, and 21 in the father. All three sons inherited one derivative chromosome from the father and in addition each inherited a different recombinant chromosome resulting in a partial trisomy 6q in the first, an apparently balanced karyotype in the second, and a partial trisomy 7q in the third son. Fluorescence in situ hybridisation (FISH) and microsatellite analysis were essential for the identification of the breakpoints. In addition, the results were confirmed by a 24-colour FISH experiment using the spectral karyotyping (SKY™) system. Paternal origin of the de novo CCR in the father was demonstrated for the first time by haplotype analysis. This is the second report of a CCR leading to simpler but unbalanced translocations in offspring as a consequence of recombination during gametogenesis, and the first report of a family case of CCR exhibiting as many as eight breakpoints in the transmitting carrier. The initial prediction that viable offspring would be quite unlikely had to be revised after the birth of three children. Genetic counselling of carriers of balanced complex rearrangements has to consider a higher probability for unbalanced recombinations than has been so far commonly assumed.

A Highly Complex Chromosomal Rearrangement between Five Chromosomes in a Healthy Female Diagnosed in Preparation for Intracytoplasmatic Sperm Injection

“…They are rarely found in phenotypically normal individuals and are usually detected in connection with reduced fertility, i.e., in-or subfertility in male carriers or recurrent miscarriages in female carriers (for review see Madan et al 1997). If fertility is maintained, the birth of a child with malformations can indicate familial occurrence of a CCR (Röthlisberger et al 1999;Berend et al 2002).…”

De novo 9-break-event in one chromosome 21 combined with a microdeletion in 21q22.11 in a mentally retarded boy with short stature

“…CCRs are rare and mostly unique findings, typically discovered by routine cytogenetics of a child with mental retardation and multiple congenital abnormalities (for overview on reviews, see Houge et al, 2003) or due to an infertility problem (Röthlisberger et al, 1999;Kuechler et al, 2003). Most cases with CCRs are de novo.…”

A complex chromosomal rearrangement with a translocation 4;10;14 in a fertile male carrier: ascertainment through an offspring with partial trisomy 14q24→1q22 and partial monosomy 4q27→q28

“…Most likely, the relatively small size of the fragment below the detection limit of 2.5 Mb in combination with the flanking high signal intensity led to the misclassification. A similar situation occurred in the family described by Röthlisberger et al (1999) with a CCR including a small insertion 7;18 and a very small translocation 18;21 (see Table 1). Both of these segments could be detected by bicolor-FISH but not by SKY due to the small size below the detection limit of the latter method (Röthlisberger et al, 1999).…”

“…The observation of Madan et al (1997) that risk estimates in familial cases of CCR should include the reproductive history of each family suggests that in the reported family the risk for another phenotypically abnormal child has to be considered significantly higher than the risk for following abortions. Röthlisberger et al (1999) 7 ND 6;10;13 3 46,XY,t(6;10;13)(p23;q11;q14) Not classified (simple 3 way)…”

“…As causes for male infertility disturbed spermatogenesis as well as pre-or postimplantation loss were suggested (Saadallah and Hulten, 1985;Madan et al, 1997;Joyce et al, 1999). There are only few reports on fertile male CCR carriers referred for cytogenetic evaluation due to spontaneous abortions of the spouses (Saadallah and Hulten, 1985;Walker et al, 1985;Gorski et al, 1988) or due to abnormal offspring (Schwanitz et al, 1978;Bourrouillou et al, 1983;Johannisson et al, 1988;Wagstaff et al, 1995;Zahed et al, 1998;Röthlisberger et al, 1999;Cai et al, 2001).…”