De novo and complex imbalanced chromosomal rearrangements revealed by array CGH in a patient with an abnormal phenotype and apparently “balanced” paracentric inversion of 14(q21q23)

Abstract

Paracentric inversions are one of the common chromosomal rearrangements typically associated with a normal phenotype. However, if dosage-sensitive genes are disrupted by the breakpoints, an abnormal phenotype could result. Detection of paracentric inversions often relies on careful high resolution banding, which has limited sensitivity. We report here cytogenetic studies performed on a 4-year-old female patient with global developmental delay, hypotonia, and dysmorphic features. The initial cytogenetic evaluation by G-banding revealed a de novo inversion of chromosome 14. Subsequent array CGH analysis using both a targeted BAC array and a high-resolution oligonucleotide array revealed microdeletions at the breakpoints of 14q21.1 (0.8 Mb) and 14q23.1 (0.9 Mb). Unexpectedly, a microdeletion in the region of 16q23.1 (1.3 Mb) was also identified, which overlaps with the common fragile site FRA16D. Parental chromosome and FISH analyses were normal, supporting the conclusion that these microdeletions were de novo in the patient and likely contributed to her abnormal phenotype. The case report presented illustrates the value of using high-resolution microarray analysis for phenotypically abnormal individuals with apparently balanced chromosomal rearrangements, including inversions.