Chromosome 13q deletion syndrome involving 13q31-qter: A case report

Abstract

Partial deletions on the long arm of chromosome 13 lead to a number of different phenotypes depending on the size and position of the deleted region. The present study investigated 2 patients with 13q terminal (13qter) deletion syndrome, which manifested as anal atresia with rectoperineal fistula, complex type congenital heart disease, esophageal hiatus hernia with gastroesophageal reflux, facial anomalies and developmental and mental retardation. Array comparative genomic hybridization identified 2 regions of deletion on chromosome 13q31-qter; 20.38 Mb in 13q31.3-qter and 12.99 Mb in 13q33.1-qter in patients 1 and 2, respectively. Comparisons between the results observed in the present study and those obtained from patients in previous studies indicate that the gene encoding ephrin B2 (EFNB2) located in the 13q33.3-q34 region, and the gene coding for endothelin receptor type B, in the 13q22.1–31.3 region, may be suitable candidate genes for the observed urogenital/anorectal anomalies. In addition, the microRNA-17-92a-1 cluster host gene and the glypican 6 gene in the 13q31.3 region, as well as EFNB2 and the collagen type IV a1 chain (COL4A1) and COL4A2 genes in the 13q33.1-q34 region may together contribute to cardiovascular disease development. It is therefore possible that these genes may be involved in the pathogenesis of complex type congenital heart disease in patients with 13q deletion syndrome.

Deletion of Chromosome 13 due to Different Rearrangements and Impact on Phenotype

“…Our male patients 2 and 3 have urogenital abnormalities, while the male patient 1, with a deletion that involves only part of the 13q34 band, has no urogenital abnormality, suggesting that the region responsible for the abnormality is within a 7.3-Mb region between positions 104.2 and 111.5 Mb in 13q33.1q34. Located in 13q33.3, the EFNB2 gene has been suggested as a candidate to play a role in male urogenital abnormalities in several studies [Dravis et al, 2004;Garcia et al, 2006;Walczak-Sztulpa et al, 2008;Kirchhoff et al, 2009;Andresen et al, 2010;Wang et al, 2017]. In fact, EFNB2 haploinsufficiency may provide a causative explanation for the observed urogenital abnormalities in our 13q deletion male patients 2 and 3.…”

“…In fact, EFNB2 haploinsufficiency may provide a causative explanation for the observed urogenital abnormalities in our 13q deletion male patients 2 and 3. Wang et al [2017] suggested the EDNRB gene, located in the 13q22.3 region, as another candidate for urogenital abnormalities. Although both our female patients carry deletions involving EDNRB , only patient 5 presents external genital hypoplasia, suggesting that this correlation is not so definitive.…”

“…Wang et al [2017] reported that the MIR17HG cluster host gene and the GPC6 gene, located in the 13q31.3 region, as well as EFNB2 , COL4A1 and COL4A2 in the 13q33.1q34 region, may contribute to cardiovascular disease development. Since cardiac defects could not be evaluated in our 2 patients (P2 and P3), whose deletions involve these last 3 genes, we cannot confirm them as causative of congenital heart defects.…”

EFNB2haploinsufficiency causes a syndromic neurodevelopmental disorder

“…In addition, Eph/ephrin signaling plays an essential role in the maintenance of several biological processes, including synaptic plasticity, angiogenesis and vasculogenesis and stem cell differentiation . EFNB2 haploinsufficiency had been involved in few human pathologies such as urogenital or anorectal anomalies …”

“…In human pathology, EFNB2 haploinsufficiency is involved in urogenital or anorectal anomalies and is suspected to be implicated in CHD or in congenital eye malformation . Few patients with partial deletions of the long arm of chromosome 13 have been reported .…”