Inverted duplication deletion of 8P: characterization by standard cytogenetic and SNP array analyses.

Inverted 8p duplication deletions are recurrent chromosomal rearrangements that most often arise through non-allelic homologous recombination (NAHR) during maternal meiosis between segmental duplications made up of the olfactory receptor (OR) gene clusters. The presence of a paracentric inversion polymorphism in 8p23.1, found in approximately 26% of European population, may trigger meiotic misalignment and NAHR between the OR gene repeats. We report clinical, cytogenetic, and molecular findings in a 4 year 8 month-old female with concomitant inverted duplication and terminal deletion of chromosome 8p. The girl, the first child of unrelated parents, was born at term, by normal delivery, after an uneventful pregnancy. Clinical examination revealed dysmorphic features, pectus excavatum, hypertonia, severe developmental delay. Brain ultrasound and MRI showed agenesis of the corpus callosum without other abnormalities. Conventional cytogenetic analysis identified additional material on chromosome 8 at band p21. SNP array analysis further characterized the abnormality as a duplication of about 31.3 Mb, from 8p23.1 to 8p11.1, and additionally revealed a terminal deletion of about 6.8 Mb, from 8p23.3 to 8p23.1. Genomic microarray also identified a region of disomy between deletion and duplication. Chromosome analysis of both parents revealed normal results. Based on clinical examination, conventional cytogenetics and SNP array, we established the diagnosis of inverted duplication deletion of 8p. SNP array analysis precisely defined the breakpoints of rearrangement and, by identifying a region of disomy between the duplication and deletion, indicated that NAHR between segmental duplications was the most likely mechanism for this type of abnormality.