Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome

Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms.Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.Chromosomal abnormalities are the most commonly recognized causes of developmental delay and mental retardation, accounting for approximately 10% of cases [1].High-resolution molecular methods, i.e. array-based comparative genomic hybridization (array-CGH) allow a careful characterization of unbalanced rearrangements, enabling a more explicit genotype/phenotype correlation [2] and enhancing the capacity to map disease-causing genes [3].Complex chromosome rearrangements (CCRs) are defined as constitutional structural chromosomal rearrangements with at least three cytogenetically visible breakpoints and exchange of genetic material between two or more chromosomes [4]. These are rare, although clinically important to recognize, because carriers can have phenotypes spanning from normal individuals, infertile males, mental retardation, to congenital abnormalities and they can be responsible for recurrent miscarriages in females [5-7].The alterations can arise de novo or be familial; familial CCRs tend to involve less chromosomes and fewer breakpoints than de novo CCRs [8]. A survey of 269371 prenatal s