ClinVar Genomic variation as it relates to human health

This CNV is a 1.15 Mb deletion of 17p13.3 on chromosome 17, (seq[GRCh37]del(17)(p13.3), chr17:g.722145_1875784), of unknown inheritance. This CNV constitutes a loss of 21 protein coding and overlaps the well-described 17p13.3 microdeletion syndrome, which includes Miller-Dieker syndrome (MDS) and isolated lissencephaly sequence (ILS). The 17p13.3 microdeletion syndrome is generally inherited in an autosomal dominant pattern, although most deletions are reported de novo. Common features of the 17p13.3 microdeletion syndrome include lissencephaly, developmental delay, intellectual disability, and seizures. Additional features in patients with MDS include craniofacial dysmorphic features and severe neurologic abnormalities. This chromosomal region is highly susceptible to rearrangements due to the presence of multiple LCRs. MDS is caused by deletions involving the PAFAH1B1 and YWHAE genes, while ILS is caused by deletion of the PAFAH1B1 gene (Dobyns et al. 2014; Blazejewski et al. 2018). Bruno et al. (2009) identified a critical region of 258 kb including both the CRK and YWHAE genes as being responsible for distinctive facial dysmorphisms associated with deletions in this region. This CNV does not result in the loss of PAFAH1B1 gene but does result in loss of both the CRK and YWHAE genes. Similar losses have not been reported in controls (Cooper et al. 2011; MacDonald et al. 2014). Based on the evidence, this CNV is classified as a variant of uncertain significance.