A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses. Case Report and Review of the Literature

Abstract

We present a complex chromosomal anomaly identified using cytogenetic and molecular methods. The child was diagnosed during the neonatal period with a multiple congenital anomalies syndrome characterized by: flattened occipital region; slight turricephaly; tall and broad forehead; hypertelorism; deep-set eyes; down slanting and short palpebral fissures; epicanthic folds; prominent nose with wide root and bulbous tip; microstomia; micro-retrognathia, large, short philtrum with prominent reliefs; low set, prominent ears; and congenital heart disease. The GTG banding karyotype showed a 46,XY,der(10)(10pter→10q26.2::4q26→4qter) chromosomal formula and his mother presented an apparently balanced reciprocal translocation: 46,XX,t(4;10)(q26;q26.2). The chromosomal anomalies of the child were confirmed by MLPA, and supplementary investigation discovered a quadruplication of the 4q35.2 region. The mother has a triplication of the same chromosomal fragment (4q35.2). Using array-CGH, we described the anomalies completely. Thus, the boy has a 71,057 kb triplication of the 4q26-q35.2 region, a 562 kb microdeletion in the 10q26.3 region, and a 795 kb quadruplication of the 4q35.2 region, while the mother presents a 795 kb triplication of the 4q35.2 region. Analyzing these data, we consider that the boy's phenotype is influenced only by the 4q partial trisomy. We compare our case with similar cases, and we review the literature data.

Keywords: 10q microdeletion; 4q partial trisomy; 4q35.2 triplication; cytogenetic analyses; multiple congenital anomalies syndrome.

Figure 1

Cranio-facial aspect of the index case.

Figure 2

Child’s karyotype 46,XY,der(10)(10pter→10q26.2::4q26→4qter).

Figure 3

Mother’s karyotype 46,XX,t(4; 10)(q26; q26.2).

Figure 4

Array-CGH test of patient—triplication of 71,057 kb in the 4q26-q35.2 region (shaded in blue). Red and blue dots represent the log2 ratio of fluorescence (Cy5/Cy3), calculated by analytical software; log2 ratio at 1 indicates a duplication of the DNA of the region (3 copies) in the test sample versus the control (in blue color), and a log2 ratio at -1 indicates a deletion of the DNA of that region in the test sample versus the control (red deviation).

Figure 5

Array-CGH test of patient—microdeletion of 562 kb in the 10q26.3 region (shaded in red). Red and blue dots represent the log2 ratio of fluorescence (Cy5/Cy3), calculated by analytical software; log2 ratio at 1 indicates a duplication of the DNA of the region (3 copies) in the test sample versus the control (in blue color) and a log2 ratio at -1 indicates a deletion of the DNA of that region in the test sample versus the control (red deviation).

Figure 6

Array-CGH test of patient—quadruplication of 795 kb in the 4q35.2 region (shaded in blue). Red and blue dots represent the log2 ratio of fluorescence (Cy5/Cy3), calculated by analytical software; log2 ratio at 1 indicates a duplication of the DNA of the region (3 copies) in the test sample versus the control (in blue color), and a log2 ratio at -1 indicates a deletion of the DNA of that region in the test sample versus the control (red deviation).

Figure 7

Array-CGH test of patient’s mother—triplication of 795 kb in the 4q35.2 region (shaded in blue). Red and blue dots represent the log2 ratio of fluorescence (Cy5/Cy3), calculated by analytical software; log2 ratio at 1 indicates a duplication of the DNA of the region (3 copies) in the test sample versus the control (in blue color) and a log2 ratio at -1 indicates a deletion of the DNA of that region in the test sample versus the control (red deviation).

Figure 8

Ideogram of chromosome 4 and distribution of breakpoints in 4q partial trisomy. Red lines represent different 4q duplications identified by different authors; blue lines represent the cases with a translocation between chromosome 4 and other chromosomes; the numbers 1–50 represent the references presented in Table 1.

Figure 9

Genome Browser image of genes in the 10q26.3 region.