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. 2021 Mar;9(3):e1592.
doi: 10.1002/mgg3.1592. Epub 2021 Jan 17.

Duplication of 9p24.3 in three unrelated patients and their phenotypes, considering affected genes, and similar recurrent variants

Zuzana Capkova  1   2 , Pavlina Capkova  1   2 , Josef Srovnal  1   3 , Katerina Adamova  1   2 , Martin Prochazka  1   2 , Marian Hajduch  3
Affiliations

Duplication of 9p24.3 in three unrelated patients and their phenotypes, considering affected genes, and similar recurrent variants

Zuzana Capkova et al. Mol Genet Genomic Med. 2021 Mar.

Abstract

Background: Recent studies suggest that duplication of the 9p24.3 chromosomal locus, which includes the DOCK8 and KANK1 genes, is associated with autism spectrum disorders (ASD), intellectual disability/developmental delay (ID/DD), learning problems, language disorders, hyperactivity, and epilepsy. Correlation between this duplication and the carrier phenotype needs further discussion.

Methods: In this study, three unrelated patients with ID/DD and ASD underwent SNP aCGH and MLPA testing. Similarities in the phenotypes of patients with 9p24.3, 15q11.2, and 16p11.2 duplications were also observed.

Results: All patients with ID/DD and ASD carried the 9p24.3 duplication and showed intragenic duplication of DOCK8. Additionally, two patients had ADHD, one was hearing impaired and obese, and one had macrocephaly. Inheritance of the 9p24.3 duplication was confirmed in one patient and his sibling. In one patient KANK1 was duplicated along with DOCK8. Carriers of 9p24.3, 15q11.2, and 16p11.2 duplications showed several phenotypic similarities, with ID/DD more strongly associated with duplication of 9p24.3 than of 15q11.2 and 16p11.2.

Conclusion: We concluded that 9p24.3 is a likely cause of ASD and ID/DD, especially in cases of DOCK8 intragenic duplication. DOCK8 is a likely causative gene, and KANK1 aberrations a modulator, of the clinical phenotype observed. Other modulators were not excluded.

Keywords: 15q11.2 duplication; 16p11.2 duplication; 9p24.3 duplication; developmental delay.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Photo of Patient 1
FIGURE 2
FIGURE 2
Graph showing the extent of DOCK8 duplications in Patients 1, 2, and 3
FIGURE 3
FIGURE 3
Photo of Patient 1’s sibling
FIGURE 4
FIGURE 4
Graph showing a comparison of the description of a 9p24.3 duplication with the duplications in Patients 1, 2, and 3
FIGURE 5
FIGURE 5
Photo of Patient 3
FIGURE 6
FIGURE 6
Graphical display of significant differences in phenotype between 9p24.3, 15q11.2, and 16p11.2 duplications and 9p24.3, 15q11.2, and 16p11.2 deletions. The data for comparison are presented in Table 3 and were analyzed using the Fisher exact test with a p value of 0.05 representing statistical significance
See this image and copyright information in PMC

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