8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature

• Main Authors: Ilaria Catusi, Maria Garzo, Anna Paola Capra, Silvana Briuglia, Chiara Baldo, Maria Paola Canevini, Rachele Cantone, Flaviana Elia, Francesca Forzano, Ornella Galesi, Enrico Grosso, Michela Malacarne, Angela Peron, Corrado Romano, Monica Saccani, Lidia Larizza, Maria Paola Recalcati
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Genes
• Subjects: 8p23.2-pter microdeletion; 8p23.3; chromosomal microarray analysis (CMA); critical microdeletion region (CR); candidate region; small deletions
• Online Access: https://www.mdpi.com/2073-4425/12/5/652

To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which <i>FBXO25</i>, <i>DLGAP2</i>, <i>CLN8</i>, <i>ARHGEF10</i> and <i>MYOM2</i> are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only <i>DLGAP2</i>, <i>CLN8</i> and <i>ARHGEF10</i> genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that <i>DLGAP2</i> is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of <i>DLGAP2</i> and better define how the two contiguous genes, <i>ARHGEF10</i> and <i>CLN8</i>, might contribute to the clinical phenotype.