7p21.3 Together With a 12p13.32 Deletion in a Patient With Microcephaly—Does 12p13.32 Locus Possibly Comprises a Candidate Gene Region for Microcephaly?

摘要

Genomic regions of copy number changes, gains and losses intermediate in size named copy number variant (CNV) are not only important source of genomic variation in the general population, but are also well-known causes of many neurodevelopmental disorders (Lee and Scherer, 2010; Weise et al., 2012). CNVs can have impact on gene/genes function via several different mechanism (Hehir-Kwa et al., 2013). Generally, assessing the clinical relevance of CNVs in cases with wide phenotypic spectrum can be challenging and should be looked as an ongoing process that can be subject to change over time (Tsuchiya et al., 2009; Hehir-Kwa et al., 2013; Palmeretal.,2014).Concomitantpresencesoftwosimultaneousinterstitialgenomiclossesarerare and in most such cases it is difficult to attribute the symptoms to one of the two affected genomic regions.However,two-hit-andcompoundheterozygosity-modelsmightbeimportantmechanisms underlying the pathogenesis in such cases (Uehara et al., 1993; Gau et al., 2012; Mascelli et al., 2014). Furthermore, selecting a single gene for further functional experiments in case of rear, large or singleton CNV can be doubtable. Recent paper by Yamasaki et al. describes how assessing and combining the influences of gene dosage sensitivity and gene expression sensitivity proper candidate genes could be selected (Yamasaki et al., 2020).