Dissection of partial 21q monosomy in different phenotypes: clinical and molecular characterization of five cases and review of the literature

Abstract

BackgroundPartial deletion of chromosome 21q is a very rare chromosomal abnormality associated with highly variable phenotypes, such as facial dysmorphic features, heart defects, seizures, psychomotor delay, and severe to mild intellectual disability, depending on the location and size of deletions. So far, three broad deletion regions of 21q have been correlated with the clinical phenotype.ResultsWe described the clinical and genetic features of three family members (father and two siblings) and other two unrelated patients with very wide range in age of diagnosis. All of them showed intellectual disability with very variable symptoms, from mild to severe, and carried 21q interstitial deletions with different sizes and position, as detected by conventional karyotype and array-CGH.ConclusionsOur study provided additional cases of partial 21q deletions, allowing to better delineate the genotype-phenotype correlations. In contrast to previous observations, we showed that deletions of the 21q proximal region are not necessarily associated with severe phenotypes and, therefore, that mild phenotypes are not exclusively related to distal deletions. To the best of our knowledge, this is the first report showing 21q deletions in adult patients associated with mild phenotypes, mainly consisting of neurobehavioral abnormalities, such as obsessive-compulsive disorders, poor social interactions and vulnerability to psychosis.

Deletion 21pterq22.11: Report of a Patient with Dysmorphic Features, Hypertonia, and Café-au-Lait Macules and Review of the Literature

“…Figure 1 F shows the deleted region in our patient compared to similar deletions in 4 patients described in the literature who present with 21q pure deletions, i.e., not associated with imbalances in other chromosomes since these would present phenotypes from both imbalances. Three of them are interstitial deletions [Lyle et al, 2009;Roberson et al, 2011;Errichiello et al, 2016], and one is a deletion due to a de novo unbalanced translocation, t(12; 21)(q24.33;q22.11), with the 21q breakpoint similar to our patient [Jespersgaard et al, 2016]. Table 1 shows the phenotypic features found in our patient and in the abovementioned 4 patients.…”

“…The phenotypic characterization of the 21q deletion is limited by the restricted number of cases reported with pure 21q deletions since some patients show monosomy 21 associated with concomitant imbalances of other chromosomes, as reported by Lyle et al [2009], Roberson et al [2011], and Errichiello et al [2016]. Furthermore, since the 21pterq22.11 deleted region contains more than 60 Refseq genes, the genotype-phenotype correlation is not so simple [Jespersgaard et al, 2016].…”

“…The resulting phenotype in partial 21q deletion is highly heterogeneous and depends not only on the size and location of the deleted segments [Ehling et al, 2004;Roberson et al, 2011;Errichiello et al, 2016;Jespersgaard et al, 2016], but sometimes also on other concomitant chromosome imbalances [Lyle et al, 2009;Roberson et al, 2011]. Lyle et al [2009] classified the patients with 21q deletions in 3 groups considering the deleted regions and their phenotypic consequences: proximal deletions (from the centromere to ∼ 31.2 Mb), interstitial deletion (31.2-36 Mb in 21q22.11), and distal deletions (from ∼ 36 to 37.5 Mb/telomere).…”

Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: Clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations

“…Molecular karyotyping was performed on DNA samples extracted from patient's peripheral blood by using a whole-genome 180 K Agilent array (Human Genome CGH Microarray, Agilent Technologies, Santa Clara, CA, USA), as we previously reported [36]. Data were analyzed by using the Agilent Genomic Workbench Standard Edition 6.5.0.58.…”

De novo mosaic and partial monosomy of chromosome 21 in a case with superior vena cava duplication

“…In general, the condition leads to an increased risk of birth defects, developmental delay and intellectual de cit. Proximal and distal deletions lead to milder phenotypes [2]. Conversely, deletions involving band 21q22 have a more severe effect on the phenotype.…”