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—Signature Client
Clinical Vignettes
Vignette 1: Prenatal Case Presentation
This case illustrates the clinical usefulness of prenatal array CGH.
A 21-year-old woman was referred at 16 weeks’ gestation because alobar holoprosencephaly (HPE) was observed on ultrasound examination. The woman’s obstetrical history revealed one spontaneous abortion and one pregnancy terminated at 15 weeks’ gestation following detection of alobar HPE. Family history showed that the father’s brother had failure to thrive and autistic features. Karyotype analysis on the mother and fetus was normal.
Microarray analysis of the fetus showed a single copy-number loss of 7.7Mb at 7q36.1q36.3 (Figure 1) encompassing the SHH gene, deletion of which is associated with holoprosencephaly 3, and a single-copy gain of 4.4Mb at 8q24.3 (Figure 2). FISH confirmed both abnormalities (Figure 3). FISH analysis of the parents showed a balanced t(7;8)(q36.3;q24.3) in the father (Figure 4). Detection of the paternal balanced translocation indicates significant risk for recurrence in this family.
Vignette 2: The Power of FISH
Here are examples of how FISH technology assists in interpreting array CGH results. Note that in each example, the array CGH finding is identical, but the FISH results are completely different.
Example 1: Abnormal microarray showing DNA dosage gain on chromosome 17p11.2.
FISH analyses of both interphase and metaphase cells demonstrate a gain (duplication) of the red probe used to represent the region of DNA dosage gain on the microarray (Figure 1). Interphase FISH clearly demonstrates three distinct signals. Metaphase FISH consistently demonstrates one red signal with greater intensity for all cells analyzed, signifying a duplication on chromosome 17p. The green signals represent control FISH probes for the subtelomeric long arm of chromosome 17.
Example 2: Abnormal microarray showing DNA dosage gain on chromosome 17p11.2.
FISH analyses of both interphase and metaphase cells demonstrate a gain (duplication) of the red probe used to represent the region of DNA dosage gain on the microarray (Figure 2). Interphase FISH clearly demonstrates three distinct signals. Metaphase FISH demonstrates two normal 17 chromosomes in addition to a marker chromosome 17p (also called a derivative 17p). The green signals represent control FISH probes for the subtelomeric long arm of chromosome 17.