A New Case with Corpus Callosum Abnormalities, Microcephaly and Seizures Associated with a 2.3-Mb 1q43-q44 Deletion

Abstract

1q44 deletion is a rare syndrome associated with facial dysmorphism and developmental delay, in particular related with expressive speech, seizures, and hypotonia (ORPHA:238769). Until today, the distinct genetic causes for the different symptoms remain not entirely clear. We present a patient with a 2.3-Mb 1q44 deletion, including AKT3, ZBTB18, and HNRNPU, who shows microcephaly, developmental delay, abnormal corpus callosum, and seizures. The genetic findings in this case and a review of the literature spotlight a region between 243 Mb and 245 Mb on chromosome 1q related to the genesis of the typical symptoms of 1q44 deletion.

Clinical and molecular characterization of 1q43q44 deletion and corpus callosum malformations: 2 new cases and literature review

“…However, the recent use of array CGH allows us to specifically pinpoint breakpoints and more accurately define a deletion and its contents [ 18 ] .…”

“…The AKT3 gene (OMIM 611,223; v-akt murine thymoma viral oncogene homolog 3 gene) encodes a serine/threonine-kinase and was found to be involved in brain development in mice [ 20 ] . Members of the AKT protein family, such as AKT3 , are implicated in numerous biological processes, including adipocyte and muscle differentiation, glycogen synthesis, glucose uptake, apoptosis, and cellular proliferation (OMIM 611,223) [ 18 ] . However, Akt3-/- KO mouse models exhibit reduced brain size and hypoplasia of the corpus callosum.…”

Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay

“…Patients with 1q41 microdeletion syndrome were reported to present with seizures, mental retardation or developmental delay, and dysmorphic features at varying degrees [60]. Another microdeletion affecting 1q43q44 was associated with corpus callosum abnormalities, microcephaly, intellectual disability, and seizures [13,21,30,45]. Of the large variety of germline mutations that have been previously associated with PMG, two mapped to chromosome 1q: AKT3 (chr1q43-44) and FH (chr1q43), [20,27,55].…”

Mirror syndromes regarding AKT3 mutations: Loss of function variant leading to microcephaly

“…On the other hand, deletions of the 1q43q44 chromosomal region, encompassing AKT3, have been reported in several individuals having microcephaly as common feature. The phenotype associated with such deletions has been reviewed in three main manuscripts (Ballif et al, 2012;Lloveras et al, 2019;Nagamani et al, 2012) which underline, as additional features of the 1q43q44 microdeletion syndrome, developmental delay/intellectual disability (DD/ID), corpus callosum dysgenesis, epilepsy, hypotonia, and facial dysmorphisms.…”