A de novo microtriplication at 4q21.21‐q21.22 in a patient with a vascular malignant hemangioma, elongated sigmoid colon, developmental delay, and absence of speech

Abstract

The widespread application of array comparative genomic hybridization (aCGH) has provided new insights into the clinical significance of copy number variations (CNVs) in the human genome. Many microdeletion syndromes have recently been linked to corresponding reciprocal microduplication syndromes related to CNVs in the same chromosomal regions. However, the extent of CNVs may not be restricted to only microduplications but may also include microtriplications or even quadruplications. 4q21 microdeletion syndrome is one of these recently described syndromes. The phenotype includes growth restriction, neonatal hypotonia, severe developmental delay, absent or delayed speech, and distinct facial features. The minimal critical deleted region, which is 1.3 Mb in size, contains the PRKG2, RASGEF1B, HNRNPD, HNRPDL, and ENOPH1 genes. Here, we report a 5.4-year-old girl with developmental delay, absence of speech, muscular hypertension, macrocephaly, a broad forehead, frontal bossing, relatively elongated extremities, a vascular malignant hemangioma in anamnesis, and elongated sigmoid colon. aCGH revealed a microtriplication at 4q21.21-q21.22 that was 1.61 Mb in size. This de novo microtriplication included nine genes (BMP3, PRKG2, RASGEF1B, HNRNPD, HNRPDL, ENOPH1, TMEM150C, LINC00575, and SCD5) and overlapped with the minimal critical region for 4q21 microdeletion syndrome. Some clinical features of the patient were similar to those of 4q21 microdeletion (macrocephaly, frontal bossing, developmental delay, absence of speech, and anxiety), whereas others were mirrored (elongated extremities and muscular hypertension). The first identified case of a de novo microtriplication at 4q21.21-q21.22 emphasizes the clinical significance of CNVs at 4q21 for patients with developmental delay and absence of speech. © 2016 Wiley Periodicals, Inc.

4q21.2q21.3 Duplication: Molecular and Neuropsychological Aspects

“…Nevertheless, a deletion encompassing different genomic loci located at chromosome 4q21 resulted in molecular and clinical definitions of the 4q21 microdeletion syndrome [ 21 - 26 ]. Furthermore, a report on microtriplication at 4q21.21-q21.22 unremarkable in the light of present study due to significant phenotypic and molecular differences, has been recently published [ 27 ]. Original research presenting the first molecular definition of the 4q21 microdeletion syndrome described 9 children with this syndrome with various microdeletions encompassing different regions of the long arm of chromosome 4: 4q21.1q21.22, 4q21.1q21.23, 4q13.3q21.21, 4q21.21q22.3, 4q21.21q21.22, 4q13.3q21.23, 4q21.21q21.23 [ 21 ].…”

Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium

“…Over 1500 children with idiopathic intellectual disability were examined as part of the European Union project “Improving Diagnoses of Mental Retardation in Children in Eastern Europe and Central Asia through Genetic Characterisation and Bioinformatics/Statistics” (CHERISH), and the RIMG identified several novel chromosomal microdeletions and microduplications [46–49]. All clinical and molecular protocols were introduced into the Genetics Clinic of the RIMG in Tomsk and are now available to patients.…”

Enolase‐phosphatase 1 acts as an oncogenic driver in glioma

“…At present, few studies have focused on the function of ENOPH1. Microdeletion at chromosome 4q21, which contains the ENOPH1 gene, can cause 4q21 microdeletion syndrome, which leads to growth restriction and severe stunting (Bhoj et al, 2013; Bonnet et al, 2010; Iourov, Zelenova, Vorsanova, Voinova, & Yurov, 2018; Komlosi et al, 2015; Lebedev, Nazarenko, Skryabin, Babushkina, & Kashevarova, 2016). Zhang et al (2016) identified ENOPH1 as a new therapeutic target for ischemic stroke.…”