Prader–Willi syndrome with atypical 15q deletion due to an unbalanced translocation between chromosomes 13 and 15

Abstract

Prader-Willi syndrome (PWS) (OMIM #176270) is a neurobehavioral disorder that is caused by various genetic mechanisms. These mechanisms include a deletion in the q11.2–q13 region of the paternal chromosome 15, maternal uniparental disomy of chromosome 15, or a pathology of gene imprinting in the proximal part of the long arm of chromosome 15. The most common cause of PWS is a 15q11.2–q13 deletion of approximately 6 Mb, which typically occurs spontaneously. However, there have been rare cases of 15q11.2–q13 deletion associated with unbalanced translocations involving chromosome 15. In order to accurately diagnose PWS and determine the mechanisms behind the chromosomal imbalance, various diagnostic methods such as conventional cytogenetics, fluorescence in situ hybridization (FISH) or microarray comparative genomic hybridization are necessary.The aim. To determine the origin of an atypical 15q deletion in a patient with Prader–Willi syndrome.Methods. Conventional cytogenetic study, FISH with DNA probes for chromosomes 13 and 15, and chromosomal microarray analysis.Results. Showed that the patient had an 8.7 Mb deletion in the 15q11.2–q13.3 region, which was found to be a consequence of a meiotic malsegregation of a reciprocal translocation between chromosomes 13 and 15 in the patient’s father. The scope of the results is in informing medical genetic counseling of patients and families with a hereditary disease.Conclusion. A comprehensive cytogenomic approach in diagnosis of genetic variations associated with Prader–Willi syndrome allows for accurate determination of copy number variations and provides information on the structure and origin of genomic imbalance. This information can be valuable for guiding medical genetic counseling and making decisions regarding future prenatal or preimplantation diagnoses.