[Cytogenetic-molecular analysis of balanced chromosomal rearrangements in nine patients with intellectual disability, dysmorphic features and congenital abnormalities].

INTRODUCTION: In about 6% of individuals with intellectual disability, dysmorphic features and congenital anomalies, an abnormal, apparently balanced karyotype is found. These abnormalities may result from abnormal expression of genes at the breakpoints, presence of a submicroscopic deletion, or other unbalanced chromosome aberrations. In such cases, the detailed analysis of breakpoints of balanced chromosome rearrangements may help with identification of genes responsible for patient's clinical features.

AIM OF WORK: Was the explanation of causes of abnormal phenotype in the carriers with abnormal but balanced karyotype.

MATERIAL AND METHODS: Cytogenetic-molecular analysis performed in nine patients with mental retardation, dysmorphic features and congenital anomalies. Studies with subtelomeric probes, high resolution comparative genomic hybridization (HR-CGH) and fluorescence in situ hybridization (FISH) with region-specific BAC clones were performed.

RESULTS: Seventeen chromosome breakpoint regions were narrowed to 200-400 kb. In one case, an 0.5-Mb submicroscopic deletion associated with more complex rearrangement has been found. Mapping of the breakpoints and information obtained from the UCSC Human Genome Browser data base enabled identification of 46 genes in these regions. Twelve genes, that may have been disrupted as a result of the patients' chromosomal rearrangement, were found. At four different breakpoints the identified genes (NRCAM, NPTX1, NMT1, MAPT, HDAC5 and MEF2C) may be due to a position effect.

CONCLUSIONS: The results confirm earlier suggestions concerning reasons of abnormal phenotype in the patients with balanced chromosome rearrangements and present the value of detailed analysis of the genome in such cases.