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Background:  Cornelia de Lange Syndrome (CdLS) is a heterogeneous disorder. Diverse expression of clinical symptoms can be caused by a variety of pathogenic variants located within the sequence of different genes correlated with the cohesin complex.   Methods:  Sixty-nine patients with confirmed clinical diagnosis of CdLS were enrolled in the study. Blood and buccal swab samples were collected for molecular studies. Mutational analysis was performed using the Next Generation (deep) Sequencing (NGS) covering 24 genes. In addition, the MLPA technique was applied to detect large rearrangements of  NIPBL .   Results:  MLPA and NGS analysis were performed in 66 (95,7%) and 67 (97,1%) patients, respectively. Large rearrangements of  NIPBL  were not identified in the studied group. Germline pathogenic variants were detected in 18 (26,1%) patients. Fourteen variants (20,3%) were identified in  NIPBL , two (2,9%) in  SMC1A , and two (2,9%) in  HDAC8 . In total, 13 (18,8%) buccal swabs were suitable for deep sequencing. Mosaic variants were found in four (30,8%; 4/13) patients negative for germline alterations. Three mosaic substitutions were detected in  NIPBL  while one in  KMT2A  gene.   Conclusions:  Comprehensive and sensitive molecular techniques allow detecting novel pathogenic variants responsible for the molecular basis of CdLS. In addition, molecular testing of different tissues should be applied since such an approach allows detect mosaic variants specific for a subgroup of CdLS patients. Finally, to test possible pathogenicity of intronic variants, RNA analysis should be conducted.

Genetic Mosaicism in a Group of Patients With Cornelia de Lange Syndrome