Direct duplication of 8p21.3?p23.1: A cytogenetic anomaly associated with developmental delay without consistent clinical features

Abstract

We report six cases in two families and a sporadic case with a direct duplication of region 8p21.3-->23.1. In one family, the duplication started in the mother and was transmitted to one son and one daughter. In the second family, the father was mosaic for the anomaly that was transmitted to his two daughters. The cytogenetic anomaly was initially described as an 8p+ with banding analysis and then delineated with fluorescence in situ hybridization (FISH) using whole-chromosome 8 painting, 8p specific painting, and 8p or 8p/8q subtelomeric probes. Deletion was not detected in the subtelomeric region of the abnormal chromosome 8 examined in one family and in the sporadic case. The phenotypic picture varies from normal to moderate mental retardation in the affected individuals. No consistent minor anomalies or congenital defects were observed among these cases. After comparing the chromosome region involved in our cases with those in others having direct or inverted duplications of 8p, it is thought that the segment 8p21.1-->21.3 might be the critical region for an 8p duplication syndrome. The parental origin of the duplication does not seem to impact its clinical significance.

Mild phenotype in a patient with mosaic del(8p)/inv dup del(8p)

“…Most patients with inv dup del(8p) have a proximal duplication breakpoint in p11.2 or p12, whereas the proximal duplication breakpoint in our patient is in distal p21.2. The same hypothesis has been proposed to explain the milder phenotypes in patients with direct interstitial 8p duplications, with or without deletions of the 8p terminus, compared to patients with the inv dup del(8p) [Fan et al, 2001;Cooke et al, 2008]. All of these direct interstitial duplications were found to be smaller than the duplications in the inv dup del(8p) cases.…”

De novo 8p21.3→ p23.3 Duplication With t(4;8)(q35;p21.3) Translocation Associated With Mental Retardation, Autism Spectrum Disorder, and Congenital Heart Defects: Case Report With Literature Review

“…More than 50 cases with 8p inverted duplication/deletion syndrome have been described but, direct duplications of chromosome 8p are less common (5,6,11).…”

“…Thus, 8p12 region was associated with MR (6), 8p23.1 region was associated with MR, ASD (16,19), facial dysmorphism, especially prominent forehead (15,18,20), and CHD (18). 8p21.3→ p23.1 region was associated with MR (5,13,14,17), ADHD (5,17), ASD (27) and CHD (5,13,21). This study shows only one case that has a large duplication involving the entire 8p21.3→ p23.1 region, associated with mild facial dysmorphism with a prominent forehead, MR, ADHD, ASD, and CHD.…”

“…The duplicated material from 8p may remain on the same chromosome or, rarer, can be translocated to a different chromosome. It seems that the phenotypic effects are not influenced by the position of the duplicated part ( 4 , 5 ). Some chromosome 8p duplications may be familial, but an appreciable number of cases result from de novo mutations ( 6 – 9 ).…”

Duplications and copy number variants of 8p23.1 are cytogenetically indistinguishable but distinct at the molecular level

“…Further FISH analysis might identify EVs as well as genuine duplications among these reported cases. Secondly, larger duplications of 8p21.3 -p23.1 have been associated with developmental or speech delay 13,14 and, in the proband of family 1 of Fan et al, 13 a complex heart defect. However, the mother and a sibling with the same duplication had no heart defects.…”