Background: Array based comparative genomic hybridization (arrayCGH) has been increasingly used as the method of choice for diagnosis of patients with unexplained developmental delay/intellectual disability (DD/ID) but is not universally available for the high throughput use in routine practice. The next-generation sequencing (NGS) techniques, emerging as a new tool in clinical diagnostics, are at present quite labour-intensive and expensive. Since multiplex ligation-dependent probe amplification (MLPA) is relatively fast, easily interpreted and cost-effective, it is still a method of choice for screening large cohorts of patients with DD/ID.
Results: We prospectively studied a cohort of 150 patients with DD/ID with or without dysmorphic features or additional congenital abnormalities. We used two distinct MLPA kits, SALSA P036 and P070, for subtelomere screening and MLPA kit SALSA P245 for the 21 common microdeletion syndromes. Subtelomere analysis was performed by both kits in all patients. All imbalances were verified by follow-up MLPA kits. The MLPA analysis revealed chromosome aberrations in 21 (14%) cases: 11 subtelomeric rearrangements and 10 microdeletions.
Conclusions: We have presented the results of the investigation of patients with DD/ID obtained by using a combination of the MLPA sets for subtelomere aberrations and microdeletion syndromes followed by the confirmation of the aberrant results by the region-specific MLPA kits. The use of two subtelomeric kits per patient and investigation of all aberrations by follow-up sets has reduced the rate of false positive and negative results and improved the diagnostic yield. The relatively low cost, simplicity and reliability makes MLPA an effective first-tier cytogenetic diagnostic test for screening large cohorts of DD/ID patients.