A complex chromosomal rearrangement with a translocation 4;10;14 in a fertile male carrier: ascertainment through an offspring with partial trisomy 14q13-->q24.1 and partial monosomy 4q27-->q28 [corrected].
Complex chromosomal rearrangements (CCRs) are usually associated with infertility or subfertility in male carriers. If fertility is maintained, there is a high risk of abnormal pregnancy outcome. Few male carriers have been identified by children presenting with mental retardation/congenital malformations (MR/CM) or by spontaneous abortions of the spouses. We report a de novo CCR with five breakpoints involving chromosomes 4, 10 and 14 in a male carrier who was ascertained through a son presenting with MR/CM due to an unbalanced karyotype with partial trisomy 14 and partial monosomy 4. The child has a healthy elder brother. In the family history no abortions were reported. No fertility treatment was necessary. Cytogenetic analysis from the affected son showed a reciprocal translocation t(4;10) with additional chromosomal material inserted between the translocation junctions in the derivative chromosome 10. The father showed the same derivative chromosome 10 but had additionally one aberrant chromosome 14. Further molecular cytogenetic analyses determined the inserted material in the aberrant chromosome 10 as derived from chromosome 14 and revealed a small translocation with material of chromosome 4 inserted into the derivative chromosome 14. Thus the phenotype of the son is supposed to be associated with a partial duplication 14q13-->q24.1 and a partial monosomy 4q27-->q28. Including our case we are aware of eleven CCR cases with fertile male carriers. In eight of these families normal offspring have been reported. We propose that exceptional CCRs in fertile male carriers might form comparatively simple pachytene configurations increasing the chance of healthy offspring.
Department of Medical Genetics, Eberhard-Karls-University of Tübingen Medical School, Tübingen, Germany.
U
U
Grasshoff
S
S
Singer
T
T
Liehr
H
H
Starke
B
B
Fode
M
M
Schöning
A
A
Dufke
D000328:Adult; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D005145:Face / Q000002:abnormalities; D005298:Fertility / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009006:Monosomy; D014178:Translocation, Genetic; D014314:Trisomy