CNV and nervous system diseases--what's new?

Abstract

Several new genomic disorders caused by copy number variation (CNV) of genes whose dosage is critical for the physiological function of the nervous system have been recently identified. Dup(7)(q11.23) patients carry duplications of the genomic region deleted in Williams-Beuren syndrome, they are characterized by prominent speech delay. The phenotypes of Potocki-Lupski syndrome and MECP2 duplication syndrome were neuropsychologically examined in detail, which revealed autism as an endophenotype and a prominent behavioral feature of these disorders. Tandem duplication of LMNB1 was reported to cause adult-onset autosomal dominant leukodystrophy. PAFAH1B1/LIS1 and YWHAE, which were deleted in isolated lissencephaly (PAFAH1B1/LIS1 alone) and Miller-Dieker syndrome (both genes), were found to be duplicated in patients with developmental delay. Finally, two novel microdeletion syndromes affecting 17q21.31 and 15q13.3, as well as their reciprocal duplications, were also identified. In this review, we provide an overview of the phenotypic manifestation of these syndromes and the rearrangements causing them.

Fig. 1

Duplications in WBS region reported to date. The uppermost illustration of the WBS genomic region including genes, markers and LCRs is modified from Cusco et al. (2008). Red arrows in the middle of the figure demonstrate the common and uncommon recurrent deletions of WBS. In the undermost part of the figure, solid green bars depict the minimal duplicated regions according to the reports. The flanking dashed lines show the possible extensions to the maximal possible duplicated segment according to the available data.