An 88.8-kb Novel Deletion of 19q13.2 Encompassing the <b><i>ATP1A3</i></b>Gene Detected by Array CGH in a Patient with Delayed Psychomotor Development, Generalized Hypotonia and Macrocephaly

Abstract

Many neurodevelopmental disorders are caused by the presence of CNVs. Chromosome microarray technology is widely used to accurately detect CNVs. We report the case of a male, aged 3 years, presenting with delayed psychomotor development, generalized hypotonia, encephalopathy, delayed myelination in the central nervous system, and poor motor coordination. The array CGH revealed an interstitial deletion of chromosome 19q13.2 with a size of 88.8 kb involving 3 OMIM genes: &lt;i&gt;RABAC1&lt;/i&gt;, &lt;i&gt;ARHGEF1&lt;/i&gt;, and &lt;i&gt;ATP1A3&lt;/i&gt;. Heterozygous mutations in the &lt;i&gt;ATP1A3&lt;/i&gt; gene are associated with delayed psychomotor development, alternating hemiplegia of childhood type 2 (AHC2), dystonia type 12, and cerebellarataxia-areflexia–pes cavus-optic atrophy-sensorineural hearing loss syndrome, also called CAPOS syndrome. The phenotypic expression of partial &lt;i&gt;ATP1A3&lt;/i&gt; deletion is, however, poorly described in the literature. The deletion was confirmed by MLPA, and we identified a hitherto undescribed novel deletion of exons 3b–21 of the &lt;i&gt;ATP1A3&lt;/i&gt; gene. Our data suggest that the deletion of the &lt;i&gt;ATP1A3&lt;/i&gt; gene is a causative factor of the AHC2 phenotype in the patient.