Prenatal Diagnosis and Molecular Cytogenetic Characterization of an Unusual Complex Structural Rearrangement in a Pregnancy Following Intracytoplasmic Sperm Injection (ICSI)

Abstract

S U M M A R YWe report on a balanced complex chromosomal aberration detected in a fetus after amniocentesis. The pregnancy was achieved after intracytoplasmic sperm injection. GTG-banding revealed a complex structurally rearranged karyotype with a translocation between chromosomes 5 and 15 and an additional paracentric inversion in the der(15) between bands 5q11.2 and 5q15. Ag-NOR staining showed an interstitial active nuclear organizer region in the der(15). Molecular cytogenetic analyses using whole-chromosomepainting probes, comparative genomic hybridization, and multicolor banding did not point to further structural aberrations or imbalances. Therefore, a complex rearrangement with three breakpoints has occurred, and the karyotype can be described as 46,XX,der(5)t(5;15) (q11.2;p12),der (15) C omplex chromosomal rearrangements (CCRs) are constitutional structural rearrangements having three or more breakpoints (Gardner and Sutherland 2004). The majority of cases reported in the literature show three-way exchanges, in which three segments from three chromosomes break off, translocate, and unite. There are very few reports on exceptional CCRs involving more than three breakpoints and/or different structural rearrangements than translocations like insertions or inversions (for review see Houge et al. 2003 and Kuechler and Claussen in this issue). A de novo, apparently balanced CCR detected at prenatal diagnosis requires exact molecular cytogenetic analysis and potentially additional molecular genetic analysis to enable proper genetic counseling. We report on the prenatal diagnosis and molecular cytogenetic characterization of an exceptional CCR in a pregnancy following intracytoplasmic sperm injection (ICSI).A 40-year-old woman was referred for prenatal diagnosis and subsequent karyotyping of amniocytes because of assisted fertilization, maternal age, and a 4-mm choroid plexus cyst. The parents had opted for ICSI after a spermiogram revealed asthenoteratozoospermia with slightly decreased sperm number and explicitly reduced sperm motility, as well as conspicuous sperm morphology. The cause of the abnormal sperm morphology and motility could not be identified, and the karyotypes of both partners were normal at a resolution level of 400 bands per haploid chromosome set in lymphocytes.Karyotyping of GTG-banded chromosomes from cultured amnion cells at the 18th week of pregnancy revealed a structurally rearranged karyotype with a derivative chromosome 5 consisting mainly of chromosome 5p material and a derivative chromosome 15 apparently composed of nearly the whole chromosome 15 and a rearranged part of the long arm of chromosome 5, presumably an inversion ( Figure 1A). This aberrant karyotype was found in all metaphases analyzed from two independent cultures, indicating that the constitutional aberrant karyotype was present

Sperm chromosome analysis in two cases of paracentric inversion

“…Then, repression may silence some genes necessary for the progression of meiosis. Furthermore, PAI may be confined to the gonads, as suggested by a recent report (19), and an abnormal spermiogram could possibly be related to gonadal mosaicism.…”

The biology of infertility: research advances and clinical challenges

“…For example, Y chromosome microdeletions present in the father will be inherited by the male offspring 156 . Not surprisingly, paternally transmitted genetic defects have been observed in offspring conceived by ICSI (Y chromosome microdeletions 135 , Robertsonian translocation 157 , translocations 158 , inversion 159 , ring chromosome 160 , renal agenesis and malformations 161 , diandric triploidy resulting from fertilization with diploid sperm (69XXY) 162 , autosomal trisomies (trisomy 13 (ref. 163), trisomy 15 (ref.…”

Exceptional Complex Chromosomal Rearrangements in Three Generations

“…WCP FISH is a highly sensitive and specific technique that can be used to identify both numerical and structural chromosomal aberrations [ 16 , 17 ], as well as cryptic genomic imbalances from individuals with apparently balanced chromosomal rearrangements [ 18 , 19 ]. This technique is a very useful and necessary tool to help characterise the CCR [ 18 – 22 ]. As shown in Figure 3 , the WCP FISH supported the karyotype findings and helped confirm the insertional rearrangement of a segment of chromosome 6q into the short arm of chromosome 4, lending support to this CCR being balanced at the cytogenetic level in the proband's mother and grandmother.…”