Isolated trisomy 7q21.2-31.31 resulting from a complex familial rearrangement involving chromosomes 7, 9 and 10

Abstract

Background: Genotype-phenotype correlations for chromosomal imbalances are often limited by overlapping effects of partial trisomy and monosomy resulting from unbalanced translocations and by poor resolution of banding analysis for breakpoint designation. Here we report the clinical features of isolated partial trisomy 7q21.2 to 7q31.31 without overlapping phenotypic effects of partial monosomy in an 8 years old girl. The breakpoints of the unbalanced rearranged chromosome 7 could be defined precisely by array-CGH and a further imbalance could be excluded. The breakpoints of the balanced rearranged chromosomes 9 and 10 were identified by microdissection of fluorescence labelled derivative chromosomes 9 and 10.

Results: The proband's mother showed a complex balanced translocation t(9;10)(p13;q23) with insertion of 7q21.2-31.31 at the translocation breakpoint at 9p13. The daughter inherited the rearranged chromosomes 9 and 10 but the normal chromosome 7 from her mother, resulting in partial trisomy 7q21.2 to 7q31.31. The phenotype of the patient consisted of marked developmental retardation, facial dysmorphism, short stature, strabism, and hyperextensible metacarpophalangeal joints.

Discussion: For better understanding of genotype-phenotype correlation a new classification of 7q duplications which will be based on findings of molecular karyotyping is needed. Therefore, the description of well-defined patients is valuable. This case shows that FISH-microdissection is of great benefit for precise breakpoint designation in balanced rearrangements.

Figure 1

The girl at the age of 7 8/12 years. Note strabism, epicanthus, down-slanting palpebral fissures and slight hypertelorism.

Figure 2

Partial karyograms after GTG-banding. A mother: 46,XX,t(9;10)(p13;q23)ins(9;7)(p13; q21.2-31.31) and B daughter: der(9)(10qter→ 10q23::7q21.2→ 7q31.31::9p13→ 9qter), der(10)(10pter→ 10q23::9p13→ 9pter) (according to ISCN 2009). The derivative chromosomes are marked by arrows.

Figure 3

Results of array CGH analysis using the Human Genome CGH Microarray 244A platform (Agilent Technologies, Santa Clara, USA), showing the internal boundaries of the duplication in 7q21q31.31 (91,941,487-120,764,345) and its exact size (28,822,858 Mb). The last normal oligonucleotide is 91,932,809 Mb and the first normal oligonucleotide is 120,770,258 Mb. The position of the array targets was mapped to the UCSC genome browser release February 2009 (GRCh37/hg19).

Figure 4

FISH-microdissection of rearranged maternal chromosomes. The origin of chromosomes was identified by whole chromosome painting probes (WCP): chromosome 7 (ice blue), chromosome 10 (purple) and chromosome 9 (yellow) are displayed and measured by the fluorescence and FISH Imaging System ISIS 3 (Metasystems, Altlußheim, Germany). The rearranged chromosomes of the balanced rearrangement are marked with circles. On the left side normal chromosomes are displayed hybridized with the labelled DNA from the microdissected chromosomes (reverse painting). Statistical analysis of the measured chromosome paintings was done using Microcal™ OriginR 6.0 (Microcal, Northampton,MA). On the very left side ideograms of the reverse painted derivative chromosomes are displayed to allow breakpoint designation.