Partial Trisomy 20qter on a Derivative Chromosome 22 in a Northern Italian Genetic Isolate with Oculo-Auriculo-Vertebral Spectrum-Related Features

Duplications of distal 20q are uncommon and the connection to oculo-auriculo-vertebral spectrum (OAVS) is still not clear. In this paper we describe a family-based cytogenetic case of a geographically isolated community in Northern Italy. Clinical data, pedigree information, and cytogenetic report from the proband were collected. Relatives were examined for OAVS-related features. Subtelomeric FISH analysis was performed with probes for 20qter and D22S1726 using peripheral blood lymphocytes to assess the rearrangement in detail. Descriptive statistics with 95% confidence intervals were computed. FISH demonstrated additional terminal material on der (22) consistent with a complex subtelomeric rearrangement and partial trisomy of 20qter. Among the 30 evaluated relatives, 15 (50.0%; exact 95% CI, 31.3–68.7) carried the rearrangement. Of these, 5 (33.3%; exact 95% CI, 11.8–61.6) exhibited features within the oculo-auriculo-vertebral spectrum, including preauricular tags, microtia or aural atresia, hemi-facial microsomia, ocular anomalies, vertebral defects, congenital heart disease, and hearing impairment. FISH does not provide information about the duplication segment or genes involved; therefore, MYT1 inclusion into the duplication cannot be confirmed and requires further chromosomal microarray, SNP-array, MLPA or genome sequencing analysis. In this pedigree, the findings support the distal 20qter/20q13.33 as a possible candidate genomic region associated with OAVS-related features and support high-resolution genomic studies and genetic counselling in affected families.