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Case Reports
. 2023 Jun 24;14(7):1333.
doi: 10.3390/genes14071333.

A Case of Class I 17p13.3 Microduplication Syndrome with Unilateral Hearing Loss

Spiros Vittas  1 , Maria Bisba  1 , Georgia Christopoulou  2 , Loukia Apostolakopoulou  3 , Roser Pons  3 , Pantelis Constantoulakis  2
Affiliations
Case Reports

A Case of Class I 17p13.3 Microduplication Syndrome with Unilateral Hearing Loss

Spiros Vittas et al. Genes (Basel). .

Abstract

17p13 is a chromosomal region characterized by genomic instability due to high gene density leading to multiple deletion and duplication events. 17p13.3 microduplication syndrome is a rare condition, reported only in 40 cases worldwide, which is found in the Miller-Dieker chromosomal region, presenting a wide range of phenotypic manifestations. Usually, the duplicated area is de novo and varies in size from 1.8 to 4.0 Mbp. Critical genes for this region are PAFAH1B1 (#601545), YWHAE (#605066), and CRK (#164762). 17p13.3 microduplication syndrome can be categorized into two classes (Class I and Class II) based on the genes that are present in the duplicated area, which lead to different phenotypes. In this report, we present a new case of Class I 17p13.3 microduplication syndrome that presents with unilateral sensorineural hearing loss. Oligonucleotide and SNP array comparative genomic hybridization (a-CGH) analysis revealed a duplication of approximately 121 Kbp on chromosome 17p13.3, which includes YWHAE and CRK genes. Whole-exome sequencing (WES) analysis confirmed the duplication. Our patient has common clinical symptoms of Class I 17p13.3 microduplication syndrome, and in addition, she has unilateral sensorineural hearing loss. Interestingly, WES analysis did not detect any mutations in genes that are associated with hearing loss. The above findings lead us to propose that hearing loss is a manifestation of 17p13.3 duplication syndrome.

Keywords: 17p13.3; WES; YHWAE; array-CGH; microduplication; neurodevelopmental disorders.

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Conflict of interest statement

The authors declare that there are no conflict of interest.

Figures

Figure 1
Figure 1
Array-CGH of the proband. Array-CGH analysis conducted using Affymetrix Cytogenetics Whole-Genome CytoScan 750K array platform according to human genome assembly GRCh37:Feb.2009 hg19. Blue box indicates the duplicated area. Array probes’ weighted log2 ratio and copy number state are also shown. Chromosomal region of the duplication is shown on the table above and on the karyogram on the right.
Figure 2
Figure 2
Cytogenetic analysis of the proband. Chromosomal analysis of peripheral blood leukocytes at banding quality of 400 bands per haploid set revealed no structural abnormalities.
Figure 3
Figure 3
Whole-exome sequencing of the proband’s DNA. 21.285 human genes were sequenced using Twist Human Core Exome EF Multiplex Complete kit of TWIST Bioscience carried on NextSeq500 by Illumina. Analysis performed by pipelines validated by Sophia DDM. Black box indicates the area of YWHAE gene that is indicative of the duplicated area (orange circles).
Figure 4
Figure 4
Comparative representation of the duplicated area between proband and her parents. Array-CGH analysis conducted using Affymetrix Cytogenetics Whole-Genome CytoScan 750K array platform according to human genome assembly GRCh37:Feb.2009 hg19. Blue box indicates the duplicated area in the proband only.
Figure 5
Figure 5
Cytogenetic analysis on peripheral blood leucocytes of proband’s mother (A) and father (B), indicating that there are no structural anomalies that could cause the duplication and, thus, classifying proband’s finding as de novo.
See this image and copyright information in PMC

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