engleski

Evaluation of chromosomal mosaicism by aCGH and MLPA: molecular characterization of mosaic ring chromosome 22

The clinical phenotype of 22q13.3 deletion syndrome may include different clinical features like developmental delay, dysmorphic face and autistic-like behavior. In case of mosaic ring chromosome 22, associated frequently with partial monosomies, variable clinical manifestations may be seen. Those are thought to be due to different sizes of deleted subregions at 22qter and the grade of mosaicism. The size of the deletion may range from none at all in asymptomatic cases, to 100 kb and more than 9Mb in symptomatic ones. In some cases mosaicism may go undetected as the presence of normal cells can mask the presence of abnormal cells ; also size of mosaics can vary in different tissues of the patients’ body. To evaluate the sensitivity of MLPA and aCGH in detecting mosaicism, we studied a de novo mosaic ring chromosome 22 in a 5 year old girl diagnosed with autism. Banding analyses revealed a karyotype mos 46, XX[58]/46, XX, r(22)(p12q13.3)[42]. FISH analysis using commercially available probes for subtelomere 22qter and all telomeres showed a terminal deletion in the ring chromosome. Further characterization of the r(22) by aCGH using Agilent SurePrintG3 Microarray 4x180K narrowed down the deletion to the distal band 22q13.3, 0.84 Mb in size. In total, 34 genes were deleted, including all genes distal from ALG12. Subsequent MLPA analysis showed a discrepancy between different kits. Two subtelomere-kits (P036 and P070) did not detect the deletion, but the Microdeletion syndrome-1-kit (P245) clearly revealed deletion of SHANK3-gene. However, Autism-1-kit (P343) only revealed decreased values for probes targeting SHANK3-gene. Here we could show that MLPA is less sensitive in detecting mosaicism than aCGH. Difficulties in the interpretation of certain MLPA probe sets are probably due to the probes present in the corresponding kits. Consequently, this can affect the diagnostic potential of MLPA technique in general and especially for detection of mosaic cases.

array CGH; MLPA; ring chromosome 22; mosaicism; FISH

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